Integrated Human Practices
Overview
The creation of genetically engineered systems should be done in a responsible, ethical, and inclusive way. This
is the focus of iGEM Integrated Human Practises. It motivates teams to interact with stakeholders, think about
more significant ramifications, and advance openness and a general understanding of synthetic biology. At every
step of the development of PathoGlow, we have assessed, communicated, and ramified our actions based on how our
project will impact the masses. As a team, we actively follow the principles of moving together and bringing
everyone closer as we walk on our path.
This year, For integrated Human practices, We spent valuable time talking to various stakeholders,
including
Scientists, Science Educators, and Science Communicators. Before we finalized the ideation and deployment of our
idea, We decided to assess the situation on the Ground level. India is a densely populated country, and being
familiar with the demographics and statistics of COVID-19 spread, we decided to explore the issue deeper by
communicating with Doctors from various Indian states. Along with the above, we conducted surveys, organized
events, and actively monitored our project's performance publicly before we finalized our ideation and Solution
to the best of our knowledge.
The Global Issue with Microbial Detection and lack of technology
The urgent need for rapid, precise, and versatile pathogen detection methods has become increasingly apparent in
an era marked by the ever-present threat of infectious diseases. A greater demand exists for technology that can
simultaneously identify several conditions with simplicity, accuracy, economy, and speed. Increases in the
prevalence of multifactorial illnesses, including diabetes, Alzheimer's, obesity, and heart disorders in recent
years, as well as microbiological infections like Schizophrenia, are problematic.
We needed to understand this problem's intricacies before we used the known concepts to design a
solution. We visualized a DNAzyme-based detection system where we can simultaneously detect various viral and
bacterial strains. Still, before we worked on it, we needed knowledge, and we had to choose a model system to
quantify the detection we were visualizing.
The problems with current detection techniques
Microbial detection technologies face several challenges, including limited specificity, time-consuming procedures, resource-intensive methods, false positive results, complexity, lack of sustainability, cost constraints, antibiotic resistance, and limited accessibility. Traditional techniques may not be suitable for emergencies, and some may produce false positives due to primer-dimer formation. Additionally, some methods may be resource-intensive and produce false positives, causing unnecessary procedures and medical expenses. Furthermore, some methods need to be more user-friendly and require extensive training. Addressing these issues is crucial for improving microbial detection.
Why did we choose to work with the COVID-19 virus?
We needed a microbial system to quantify the detection system we had in vision. Initially, detection was a
significant obstacle in a project, particularly in identifying pathogens like viruses or bacteria. Overcoming
this challenge was crucial for the project's success and progress towards its objectives. We already had a
vision to work with an infectious disease that affected the masses hugely and had a significant impact on the
global population. As we explored different disease-causing microbes, such as Plasmodium falciparum and
Salmonella Typhi, We realized that no other microbe would be a better target than the coronavirus. Seeing how
much the pandemic affected our lives as students and changed our vision about infectious disease starting in
2019, we were confident that the COVID-19 virus could be the perfect system for us to work with.
The various other reasons our team chose to work with COVID-19 were Its unique strains, high
infectiousness, high lethality, and high mutations. A specific detection platform is needed to distinguish
between different themes, control their spread, and adapt to the virus's dynamic nature. We thus aimed to
develop our project to address these challenges and contribute to improved pathogen detection using our concept
of organic logic circuits and DNA-based enzymes. The virus's high lethality and mutations necessitate a
versatile detection method, and we decided to work with the Coronavirus. But before we embarked on the journey
of WetLab and scientific experimentation, we had to understand and acknowledge what our detection system would
face. We as a team understood that before we worked on any disease, we needed to deeply understand who is the
targetted stakeholder, how our project would impact the public, and what changes could be made as we developed
our kit.
Understanding the Pandemic on the Ground level
The entire world faced a huge challenge as we faced a Global pandemic. In the latter half of 2019, the new
coronavirus SARS-CoV-2 that triggered the worldwide COVID-19 pandemic arose. Millions were affected globally as
a result of its quick spread. Governments established lockdowns, travel restrictions, and vaccination efforts to
lessen its effects. The epidemic brought significant physical, economic, and social problems, which impacted
society worldwide.
With 44,998,838 recorded instances of COVID-19 infection, India has the second-highest number of confirmed cases
in the world (after the United States of America). With 532,032 fatalities, India has the third-highest number
of COVID-19 deaths in the world (behind the United States and Brazil). The World Health Organisation estimates
that 4.7 million more fatalities, directly and indirectly connected to COVID-19, occurred in India in October
2021.
The primary stakeholders, apart from those affected by the disease, were doctors, nurses, and healthcare
providers who had the first view of the ground-level situation of the rising pandemic. To understand our
responsibility while developing Pathoglow, we interviewed several doctors from different states of India who had
a first-hand view of the infection and the first connection with the affected masses. We decided to go forward
on a mission to understand what doctors from different states of India need and expect from us. What are the
primary stakeholders' challenges, and what expectations do they hold from a new detection system? As we
collected the opinions from doctors and healthcare workers, we understood that our detection kit should not only
be accurate, it should be convenient to use, should give timely results, should be accessible, and also
cost-friendly so that the lower strata of the population is not devoid of the facility.
UP
Engage:
Our team contacted Dr. AK Gupta, who served as the Additional Chief Medical Officer and headed COVID-19 management in the Kanpur zone of Uttar Pradesh, India, during the pandemic. Our objectives included gaining insights into health management strategies employed during the pandemic and assessing public awareness. Additionally, we sought to uncover Dr. Gupta's vision for addressing future pandemics and identifying potential improvements in handling such situations.
Anticipate:
COVID-19 thrived in densely populated cities of Uttar Pradesh and had spread rapidly due to inadequate
healthcare infrastructure and hospital constraints, resulting in a significant loss of life.
The general public faced substantial challenges in accessing COVID-19 detection methods due to an
overwhelming caseload. Both RT-PCR and antigen testing, the primary techniques, suffered from accuracy
issues or delayed results (often taking 7-10 days due to the caseload). Isolation or dedicated ward
allocation occurred only after confirming a positive diagnosis, inadvertently contributing to further
infections.
There was a pressing need for heightened public awareness. Many individuals experienced psychosomatic
issues due to widespread fear stemming from this novel and unfamiliar infection. Dr. Gupta aptly stated,
"Being COVID positive was not a curse. The panic created due to lack of awareness was."
Reflect:
Following our discussion, it's evident that an urgent need exists for a rapid, accurate detection kit. With the swift, often asymptomatic nature of infections like COVID-19, accessible self-diagnostic kits can help reduce the burden on testing labs. Additionally, our efforts should expand to cover a wider range of pathogens, and we must prioritize raising awareness about general health and immunity development, especially in underserved communities.
Act:
Our kit's development focuses on affordability without compromising accuracy, making it more cost-effective than existing self-diagnostic kits in the market. Leveraging our highly modular system, we can swiftly create new kits to detect emerging pathogens or various strains of the same pathogen. Furthermore, Darpan, the drama club of IISER Mohali, played a pivotal role in promoting healthcare, hygiene, and infection awareness among the underprivileged working class at IISER Mohali.
Engage:
We contacted Dr. Ripudaman Biya from Rajasthan, India, to gather information on the state's pandemic situation. Our goal was to obtain a detailed account of the challenges faced by Rajasthan during the pandemic, including issues experienced by the general public. We also sought insights into the ideal characteristics of a detection kit and assessed the level of disease awareness and awareness of government facilities among the lower socioeconomic segments of society.
Anticipate:
The COVID-19 virus was extremely contagiousness and had spread rapidly through the soceity. Hospitals
encountered significant challenges during the pandemic, where only 2-3 confirmed cases per 100 patients
became potential sources of infection, unintentionally transmitting the virus to other patients and
healthcare workers. Moreover, the rapid antigen test, which takes 2-3 hours to deliver results,
exhibited a concerning rate of false positives, leading to the misidentification of some initially
labeled as COVID-negative patients as COVID-positive, thereby exacerbating the problem.
The COVID-19 pandemic had posed substantial challenges to the public, especially in terms of early
detection. While isolating COVID-19-positive individuals can be instrumental in mitigating the issue,
the occurrence of false positives has the potential to contribute to further virus transmission.
Furthermore, a significant portion of the population refrains from seeking medical care, with only 10 to
15% having the means to afford treatment. This problem was further aggravated during the COVID-19
pandemic due to confusion regarding where to seek necessary assistance.
An important perspective
shared by Dr. Ripudaman emphasizes, "If we can promptly detect the virus, even in asymptomatic patients,
we can proactively initiate isolation and treatment measures."
Reflect:
Accurate and sensitive kits are needed to reduce the false reported cases. At the same time, these kits should be readily available to avoid any detection delays. Raising public awareness is extremely essential to bridge the gap between the people and the services and treatment that are readily available for them. Classification of patients on the basis of severity is essential to enable efficient deployment of resources to provide better and timely treatment for all
Act:
We have fine tuned our system depending on the context of deployment. While a lab setting for quantitative analysis is extremely precise, the qualitative aspect will also have a fine balance between accuracy and precision. The development and deployment of these kits are using already established techniques, it is the product of these production techniques that make our project novel. The quantitative as well as specific nature of our system not only helps us to estimate the pathogen load in the sample but also identify which strain the infection belongs to, thus helping us to provide for strain specific detection. Addressed towards the underprivileged working class of our institute, IISER Mohali, we had organized a skit with the help of the drama club, Darpan, to spread awareness about infections and how to maintain hygine
Rajasthan
Kerala
Engage:
Dr. Mridula Ravunny, a medical officer at CHC Edayazham in Kottayam, Kerala, engaged in a discussion with us regarding the limitations of the current system model in use. She also explored the feasibility and potential significance of our proposed model.
Anticipate:
Dr. Mridula Ravunny addressed several crucial aspects during our conversation. Firstly, she highlighted
the uncomfortable procedure of phlegm collection, emphasizing that patients often exhibit reluctance
when symptoms are minor and also the arduousness in its transport to the laboratory since if not
received in proper condition, it makes the diagnosis difficult to perform.
Additionally, Dr. Ravunny discussed the time-consuming nature of RT-PCR as well as the associated issues
with sample collection and transportation during the pandemic. Delays in movement adversely affected
other procedures, leading to overall inefficiencies. She stressed that early diagnosis is paramount for
effective pandemic prevention.
Furthermore, she noted that COVID-19 arrived in waves, making
strain-specific detection less helpful during the initial phases when the specific strain was unknown.
However, she emphasized the potential value of strain-specific detection for future outbreaks once the
specific strain is identified.
Reflect:
The time taken for each step to be done is a big issue. We need to devise a model that is quicker.
Transportation of materials between labs and movement between one lab to another took a lot of time.
Better to devise some strategy that makes the entire detection process simple enough to be done and
detected in one location.
Act:
Development of the deployed kit is such that it requires only a few steps and in most cases will require no instrument for pre-processing. Development of the same system in a quantitative as well as qualitative kit requiring no instruments would help to perform a preliminary round of detections among the population which will help identify and isolate the infected crowds thus making control of disease spread and subsequent treatments much more efficient to deploy.
Engage:
We had an insightful discussion with Dr. Sachin Sudade of Madhuprema General Hospital in Pune, Maharashtra, concerning the impact of the pandemic in the state. Our conversation encompassed the challenges faced by healthcare professionals, the disruptions in their lives, and the potential remedies to address these issues.
Anticipate:
Dr. Sachin discussed the extended reporting times, which occasionally exceeded 48 hours. He underscored
the significance of early clinical detection and expedited laboratory results, emphasizing the
substantial impact these factors could have during pandemic situations.
Additionally, he addressed the social stigma that was rampant in the general population. The
isolation doctors experienced from their communities due to their exposure to patients was a poignant
and challenging aspect for healthcare professionals dedicated to their work.
Reflect:
Quicker detection and a method that would give faster results is needed. We should communicate science with the commoners and try to spread awareness against the stigma that is prevalent in society
Act:
Our kit is also developed as a qualitative test to increase the number of self diagnosis thus reducing the load of lab testing with hopes of increasing the speed with which the lab test results are produced. We planned a drama that would showcase health care and try to pull out the misconceptions and stigma in society
Maharashtra
Exploring different view points:
Most of the low-income people in our area and nationwide are subjected to subpar hygienic
conditions, contaminated food, and subpar drinkable water. According to the WHO, unhealthy food costs low- and
middle-income countries like India 110 billion USD annually in lost productivity and medical costs. Seeing the
challenges faced by the population, the ideation of a detection system that is convenient and practically
deployable would be a tough challenge for us. We decided to discuss the ideation and implementation of our
proposed solution along with the science behind the spread of the virus from various Scientists and people
working with infectious diseases to understand what we will be dealing with as we proceed with the Science.
As we conducted our interviews with some of our country's prominent scientists and virologists, we realized the
challenges we could face working with a viral genome. The COVID-19 genome is complex due to its size, rapid
mutations, RNA nature, high contagiousness, bioinformatics challenges, and the need for international
collaboration. Its large size, rapid mutations, and RNA nature complicate sample handling and analysis. The
virus's high contagiousness necessitates extreme care in biosafety labs, adding complexity and cost to research.
Advanced bioinformatics tools are required for interpreting genomic data. Even though the challenges were real,
With the series of interviews and collective viewpoints, we had solutions to most of the problems. We had
valuable suggestions on how to proceed with developing our Detection kit, and we were ready to embark on the
scientific ideation of the project.
Dr. Rhitoban Ray Choudhury
PGIMER Chandigarh
Engage:
We reached out to Dr. Rhitoban Ray Choudhury, a specialist in evolutionary biology with extensive expertise in genetics and genomics, to seek his professional insights regarding the diverse strains of the same pathogens and various other diseases, not limited to COVID-19. We sought to understand their impact on society and the diagnostic approaches used for these diseases.
Anticipate:
An important aspect of COVID-19 is that it is seasonal and cannot be removed; we must plan for its
changes. Delta was the most dangerous, whereas Omicron was less lethal but extremely contagious.
Detecting strains is dependent on identifying genetic differences, which is difficult owing to fast
virus mutation. "Finding a single snip based detection is almost impossible," he says scientifically.
This is due to viruses' fast mutation, which causes them to modify these snips the moment a kit is
released.
Plasmodium vivax (least fatal) causes 99% of malaria cases in India, but Plasmodium falciparum (very
dangerous if not treated within a month) causes 1%. Although microscopy is the best standard, the
scarcity of slides for falciparum comparison delays diagnosis and increases mortality.
Reflect:
We recognized the need of having a systematic approach for performing stain specific detection. Starting
from a broader field of if it is even an infection of a particular species and then moving forward
stepwise to detect the strain is essential.
The system we develop is essential to give accurate and timely results, relative to the current standard
in cases of microscopy detection of malaria to even stand a chance to be better than the current methods
Act:
Exploiting the modular nature of our system, the different loops will be designed in such a way so that
initially it will check on a broader field of which disease it is and then increase in specificity of
which strain the infection belongs to.
Since the system remains more or less the same, just the recognition loops vary, the protocol for
detection irrespective of what disease is there, remains extremely similar thus it helps to have same
times for detection of any disease
Engage:
We had decided to engage in a conversation with Dr. Indranil Banerjee, a specialist in cellular virology. Our objective was to seek his professional insights, opinions, and recommendations, not only regarding our project but also concerning the future of viral pathogenesis and detection.
Anticipate:
During our conversation, Dr. Banerjee emphasized the need of distinguishing unique pathogenic strains
associated with various viruses. He highlighted the need of identifying strains that could potentially
represent a hazard. This effect was particularly visible in the case of COVID-19, where a plethora of
variations appeared in a relatively short period of time. These mutations exhibited a distinct pattern
of lower lethality but increased infectivity. For example, the Omicron form, despite infecting a large
number of people, had a lower death rate than the Delta variant.
An innovative way to plan for future pandemics has been presented. In the words of Dr. Banerjee, "From
my perspective, rather than directly targeting the virus itself - which will inevitably undergo
continual mutation and change in form - if we can identify the pivotal molecules and pathways upon which
the virus relies, which will allow us to potentially neutralize infections caused by
yet-to-be-discovered viruses in the future. ."
Reflect:
While strain specific detection is important to prepare the type of treatment that will be needed, it is
essential to generate reliable data that can help plan strategies for better management of future
pandemics
We also appreciate a different approach to what is done for detecting viruses. While our method works in
a novel way, it still targets the same markers as is done in current methods. We should identify and
make multiple different systems to target these unique markers leading to more efficient detection, with
a single kit identifying multiple different viral infections
Act:
We will integrate identifying common factor associated with viral infections into our software. Along with this we will look into the possibilities of having strand-displacement aptamers for protein detection as our activating loops, with hopes that the same system can detect not just RNAs and DNAs but proteins as well, leading to more efficient kit development and reduce in wastes and costs.
Dr Indranil Banerjee
Identifying and Formulating a Solution
Our study and in-depth conversations with subject-matter specialists led us to conclude that delayed microbial
identification posed substantial complexity. We sought to develop a complete solution, influenced by the
insightful opinions of stakeholders, to successfully solve this issue.
We were able to create essential project criteria thanks to the valuable insights into their issues and
experiences that came from our engagement with stakeholders. We decided that the best course of action was to:
1. Rapid: Getting results quickly was essential for timely reactions to potential threats.
2. Sustainability: Sustainability was a key factor, emphasizing long-lasting, eco-friendly solutions.
3. Accuracy: To prevent false positives or negatives, accuracy in microbiological detection was essential.
4. User-friendly: Simplicity was crucial to ensuring that it was usable by users of all skill levels.
Developing a novel technology that fulfills our Objectives
With a vision of Detection system based on DNAzymes in mind,we had to develop a technology that fulfills our primary objectives.
Highly Specific Detection:
Our main goal is to create a platform to locate and identify unique DNA and RNA sequences precisely. We see this platform as a potent instrument with unmatched accuracy for detecting pathogens, thanks to its ability to distinguish between closely related strains and variations.
Simultaneous Detection:
Traditional detection techniques sometimes require independent testing for every target sequence, which can be time- and resource-consuming. By making our technology capable of concurrently detecting several lines, we want to push the efficiency limits while expanding its potential uses beyond pathogen detection.
RNA compatibility:
Because of their genetic makeup, RNA-based diseases, such as certain viruses, offer particular difficulties. We are committed to making our platform compatible with reverse transcription amplified RNA sequences to provide sensitivity levels comparable to quantitative PCR (qPCR) while providing findings that are obtained much more quickly.
Primer-dimer formation is a common problem with PCR-based detection techniques, frequently resulting in false-positive findings. Our strategy successfully tackles this issue, guaranteeing the precision and dependability of our platform’s results.The core of our Idea
Our project's novel utilization of DNAzymes is its foundation. These are three manufactured recognition loops (RecLoops) made of single-stranded DNA. The DNAzyme's secondary structure resembles a 'T '-shaped molecule with loops on each end. Due to strand overlap, a portion of the top arms is concealed. This masking DNA strand is displaced (also known as strand displacement) when two distinct and complementary sequences bind to the RecLoop regions. This enables the substrate/probe, which complements the concealed area, to be revealed and hybridized with that region. A fluorophore and a quencher are both included in the probe. The distance between the fluorophore and quencher is widened during hybridization. This enables the molecule to turn fluorescent and provide a signal. With the help of a deactivation sequence in a third loop, we can precisely regulate the DNAzyme's activity. This distinctive characteristic gives our platform the ability to make rational decisions. Practically, only the presence of two particular sequences (recSeq) results in a positive signal. This makes it possible for us to distinguish between strains with only two recSeqs and those with all three recSeqs.
Ideation and Designing
When developing our solution, we involved experts during the creativity and design stages. This was done to make sure that their comments and the stakeholders' values were represented in our solution. disorders.
Professor Bachhawat
PGIMER Chandigarh
Engage:
A biochemist and synthetic biology enthusiast, Professor Bachhawat was the first person we contacted to gather inputs about the impact of the COVID-19 pandemic and the significance of rapidly developing highly accurate and specific kits.
Anticipate:
He believes that the commercial availability of strain-specific detection would be highly beneficial as
it would "facilitate the discovery of correlations between genotype and phenotype, subsequently aiding
in treatment. This would enable us to discern critical distinctions between strains, which are essential
for distinguishing the significant from the less significant."
The major issue in this pandemic,
one that should not be repeated in future pandemics, is the delayed commencement of research and action.
"The starting point should be quick."
Reflect:
We acknowledge the importance of strain specific detection and the necessity to fine tune our system to increase its specificity. Along with this, it is essential to fast track the development of new kits for new pathogens as and when they arise.
Act:
We have identified regions of our DNAzyme that can be modified to increase specificity without compromising on accuracy. The software enables us to identify unique sequences associated with a new pathogen once it is sequenced. Since our system is highly modular, we will be able to exploit this for detection of different strains of the same pathogen
Engage:
Dr. Ajit Dua, CEO of Punjab Biotechnology Incubator and an expert in Food Quality, Safety, and Authenticity, provided us with valuable insights into the feasibility of our project. She highlighted the key areas we should prioritize in order to enhance our project and transform it into a viable product ready for market deployment.
Anticipate:
She emphasized on the need of automation to reduce the dependence of our systems on trained human resources. “If manual steps of the machine can be avoided then we can utilize the human resources in a better way for interpretation of the results, data and the activity where actually human input is needed” Rapid Analytical Food Testing Kits and Equipment are need of the hour. FSSAI has an established system of approving such RAFT Kits/equipment after rigorous review.
Reflect:
It beneficial if the system could have a high degree of automation. For this, the number of steps as well as the complexity of each step should be kept low. Since only qualitative testing is needed for multiple pathogens in food and water context, if our system can simulate multiplexing, like detecting salmonella and E. coli O157, in one go, it will help in faster and easier detection of contamination in water sources and seeds for crops.
Act:
The deployment of the system was thought to be done in such a way, the steps require very less human i nput while the analysis has ample scope for automation. Development of software to incorporate strand displacement aptamers into our system enables us to detect not only DNA and RNA but also proteins. A mix and match of the recognition sites enable us to perform a variety of detections in one go.
Dr. Ajit Dua
Our proposed Implementation
We analyzed our project in light of the values we chose to prioritize at each level of its development to close the loop and ensure that our solution aligns with stakeholder needs.
Our team evaluated the suggested implementation after developing a concept and building a solution based on the
advice and experience of wet and dry lab specialists and the values of our stakeholders. The scientific approach
that is most immediately obvious is the one that is proposed to be used. Due to the impact of late diagnosis and
synchronization with the cycle of infectious illnesses and their transmission patterns, synthetic biology
solutions are necessary.
However, before a synthetic biology-based solution is presented, a few problems must be overcome. The importance
of taking into account all technological, safety, ethical, and sociocultural factors was highly valued by our
team. From the beginning of our IHP adventure, we were firmly dedicated to a human-centered approach. The people
we contacted and the ensuing conversations have significantly impacted our research.
We understood that the realization of the envisioned project, a crucial stage in our scientific path with
significant public awareness, deserved no less focus. We turned back to the people who started this project and
contributed to its founding ideas as we began this pivotal phase. These discussions significantly influenced our
judgments about ethics, technological considerations, safety precautions, and communication techniques at this
project stage. They ensured that our ultimate answer was morally correct and helpful to everyone.
Social and Ethical perspective of our Project-
Organic logic circuits and PATHOGLOW's novel DNAzyme-based pathogen detection technologies are exciting
developments with broad societal and ethical ramifications. Our research improves the security and health of the
entire world by addressing the essential need for quick and accurate infection detection. The capacity to
concurrently identify various pathogens will speed up diagnosis and help with prompt containment and treatment,
reducing the spread of infectious illnesses.
By preventing the development of primer dimers, findings are guaranteed to be accurate, lowering the possibility
of false positives and unneeded anxiety. Our initiative prioritizes sensitivity and specificity in an ethical
environment, reducing the likelihood of incorrect diagnoses and encouraging ethical medical procedures. Our
technology's adaptability goes beyond disease detection, having potential uses in various fields.
We agree that research contributes to human well-being. However, a human-centered design involves much more than
just paying attention to people. Understanding the social context is necessary. Knowing the appropriate
questions to ask is essential. At this moment, the interaction of people and science was the focus of our
investigation. How might scientists address social problems more effectively and consider people's opinions
while developing solutions?
Opening up dialogues with ethicists and social scientists significantly influenced how our research was
developed. They taught us how to frame the problem inside the usually difficult conversations that society and
synthetic biology have previously had about these challenges. These conversations helped us listen to people and
thoughtfully and meaningfully include them in the creation of our program.
References
- Current challenges in identification of clinical characteristics and detection of COVID-19: A comprehensive review - ScienceDirect
- COVID-19 pandemic in India - Wikipedia
- COVID-19 Diagnostics, Tools, and Prevention - PMC (nih.gov)
- Coronavirus: a comparative analysis of detection technologies in the wake of emerging variants.
- Testing at scale during the COVID-19 pandemic.
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