Team:Elan Vital Korea/Practices








HUMAN PRACTICE


PRACTICES

-Focus-

-Integrated Human Practice-

-Education & Public Awareness-

FOCUS




EXECUTIVE SUMMARY & OUR FOCUS

Korea may be famous for internet startups and K-Pops, but not for synthetic biology. Synthetic biology has a huge potential for improving the welfare of humanity, but being such a young discipline, at the same time has many issues yet to be resolved, including ethical, legal concerns and safety issues. In US or EU, thus, it is not uncommon to see close cooperation between the government and private enterprises to create an ideal research environment and efficient legal and regulatory framework.

No such environment exists in Korea, at least up to the level of efficiency found in US or EU. We have concluded that the policy makers and important players (such as colleges and research institutes) must be better informed of the new field so as to provide an environment that is favorable for the advancement of synthetic biology while safe enough to prevent hazardous events. We have also identified that it is necessary to promote fundamental concepts of synthetic biology to younger generations, including high school students and younger. Keeping these social environment of Korea in mind, Elan Vital Korea has established 5 goals for our human practice activities:
- first, enhancing public awareness of the synthetic biology;
- second, promoting the importance of the field to policy makers, research institutes and journalists;
- third, promoting the public awareness of the importance of the early detection of contagious pathogens;
- fourth, putting safety first for our projects;
- and finally, close cooperation and co-work with other iGEMers in Korea.







First, we continuously and strenuously strived to enhance the public awareness of the synthetic biology, especially among younger generations. We have participated in Korea Youth Expo and operated a booth (from May 22 to May 24), and worked hard to communicate with participants in 2015 Science Festival (from July 27 to August 2). We offered basic education sessions on DNA and synthetic biology, and conducted surveys to better understand the level of general awareness of the synthetic biology and iGEM. Based on the information and data we gathered from them, we have developed the long-term education plan for primary and secondary school students. We have reached the National Science Teachers’ Association of Korea, with more than 2,400 science teachers as its members, and established a communication and cooperation network. We have provided some materials for use for education including blogs, Youtube videos, lecture videos, booklets, brochures and simple DNA extraction kits, etc.



Second, we have learned that policy makers and education and research bodies in Korea are not sufficiently informed of the recent developments of the synthetic biology, which resulted in lack of proper safety guidelines and articulation of legal, ethical and environmental implication-related discussions and awareness. In an effort to change the condition, we have drafted the report of our findings and suggestions, and sent our concerns and recommendations to politicians (including members of the National Assembly of Korea) in charge of science and technology-related policymaking. In the process of researching the current policy environments and developing recommendations, we have contacted universities, research institutions and small- and medium-size enterprises in order to better understand their concerns. We have also contacted journalists, who function as major contact point to the general public. We have distributed summaries of the synthetic biology and iGEM. In the process, we have persuaded some of them to be our sponsors.





Third, we have developed the public awareness strategy for our project, “Early Detection of Antibiotic Resistant Bacteria Using Quorum Sensing”. Incidentally, Korea has been hit hard by MERS virus as late as June this year, which greatly heightened the public awareness – and fear – of the contagious pathogens, as well as the need to learn more of the cause and cure for those dreadful diseases. We began our public awareness campaign by researching and studying the current methods of detecting and tackling the antibiotic-resistant bacteria from Korean CDC, hospital guidelines and related research papers. We have discovered that, compared to the strict and detailed action plan in place by the US CDC, the Korean CDC has not – yet – established networks of hospitals and nursing homes that need to be closely monitored and promptly intervened as need arises. Based on this finding, we have drafted letters and papers and sent them to Korean CDC and safety committees of hospitals. We plan to continue our efforts on this area.



Fourth, we have put the strongest emphasis on the safe implementation of our project. Our project belongs to Risk Group 1, but we have observed the lab safety rules and guidelines very tightly, and promoted the importance of observing the lab safety based on deeper understanding of the biosafety guidelines. We have developed the Youtube video explaining the biosafety levels, and encouraged people in lab environment to watch it. Finally, in an effort to promote the spirit of cooperation, sharing and mutual contribution of iGEM, we have reached out to other teams joining the iGEM Jamboree, and hosted regional meet-up. Even before and after the regional meet-up, we held discussions and mentorship with Korea University team on lab works and iGEM experiences. We also met with HAFS team and provided assistance on parts submission and using BioBricks and other materials included in the Kit. We have shared with them our failure and misunderstanding we had experienced last year which, we hope, would be entertaining if not informative.


To The Top
Integrated Human Practice

Threat of Antibiotics-Resistance and Countermeasures: Korea and US

The spread of antibiotic-resistant bacteria is a global health problem that affects nations across borders and boundaries and rapidly spreads throughout the world. These nightmare bacteria pose catastrophic threat to people everywhere in the world.

Our project is Early Detection of Antibiotic Resistant Bacteria using Quorum Sensing. It is closed related to the surveillance and containment of the pathogens. With the understanding, we have conducted case study of Korea and the US on the current status of antibiotic resistant bacteria infection and the countermeasures. We have gathered data on the spread of antibiotic-resistant bacteria and countermeasures taken as well as contemplated in Korea and the US. For this, we have relied on various materials and documentations, and some of them are translated from Korean.

Introduction

On November 11, 1945, Alexander Fleming delivered his Nobel Prize speech. This great man who discovered penicillin warned that bacteria could become resistant to these remarkable drugs. Indeed, the development of each new antibacterial drug has been followed by the detection of resistance to it. The development of resistance is a normal evolutionary process for microorganisms, but it is accelerated by the selective pressure exerted by widespread use of antibacterial drugs. Resistant strains are able to propagate and spread where there is non-compliance with infection prevention and control measures.


Even considering regional discrepancy in the data quality as well as quantity, resistance patterns for the bacteria of public health importance is sufficient to alarm the world. For example, the proportion resistant of S.aureus to commonly used specific antibiotic drugs exceeded 50% in many countries. Furthermore, there are limitations in effective oral treatment options for some common community-acquired infections in several countries, and that there remain few, if any, treatment options for some common severe and health-care associated infections in many places.

High rates of MRSA imply that treatment for suspected or verified severe S. aureus infections, such as common skin and wound infections, must rely on secondline drugs in many countries, and that standard prophylaxis with first-line drugs for orthopaedic and other surgical procedures will have limited effect in many settings. Second-line drugs for S. aureus are more expensive; also, they have severe side-effects for which monitoring during treatment is advisable, increasing costs even further.

Unfortunately, there is at present no global consensus on methodology and data collection for Antibiotic Resistant Bacteria surveillance. Routine surveillance in most countries is often based on samples taken from patients with severe infections – particularly infections associated with health care, and those in which first-line treatment has failed. Community-acquired infections are almost certainly underrepresented among samples, leading to gaps in coverage of important patient groups.

It is urgent to develop effective implementation strategies in order to curtail the emergence and spread of AR, and to evaluate the effect of interventions.

Antibiotic resistance has a significant adverse impact on clinical outcomes and leads to higher costs due to consumption of health-care resources. Patients with infections caused by bacteria resistant to a specific antibacterial drug generally have an increased risk of worse clinical outcomes and death, and consume more healthcare resources, than patients infected with the same bacteria not demonstrating the resistance pattern in question.

Although surveillance on antibiotic resistant bacteria has been undertaken for many years in a number of high-income countries, there are still large gaps in knowledge about the status of surveillance capacities worldwide, particularly in resource-limited settings.

Available data are insufficient to estimate the wider societal impact and economic implications when effective treatment for an infection is completely lost as a result of resistance to all available drugs. The overall health and economic burden resulting from acquired antibiotic resistant bacteria cannot be fully assessed with the presently available data; new methodologies are needed to more precisely assess the total impact of resistance, to better inform health policies and to prioritize the deployment of resources. However, even admitting the lack of reliable information on the financials, the overall cost is highly burden to all nations, even further to the less developed countries. For example, the yearly cost to the US health system alone has been estimated at US $21 to $34 billion dollars, accompanied by more than 8 million additional days in hospital. Because antibiotic resistant bacteria has effects far beyond the health sector, it was projected, nearly 10 years ago, to cause a fall in real gross domestic product (GDP) of 0.4% to 1.6%, which translates into many billions of today’s dollars globally.



KOREA

In Korea, Korean CDC collected antibiotic-resistance infection cases from hospitals, which shows that 41,883 patients (about 7% of the total hospitalized patients) were infected by antibiotic-resistant bacteria during the first half-year of 2014 (from January 1 to June 30, 2014).

(Source: Korea Center for Disease Control and Prevention, http://www.cdc.go.kr/search/sEngine.jsp?kwd=MRSA%EA%B0 %90%EC%97%BC)

KARMS released annual report in 2014 containing antibiotic resistance infection data gathered from hospitals as well as long term care facilities and small & medium sized clinics. Publishing such data is a clear evidence that the Korean government is keenly aware of the hazards of the antibiotic resistant bacteria and also shows its commitment to deal with the matter systematically. The government adopted a law on the Prevention and Containment of Infectious Diseases in Dec. 2010.

In accordance with the executive order of the law, antibiotic resistance infections including VRSA, VRE, MRSA, MRPA, MRAB, CRE were designated as “infections to be contained”. The annual reports deals with S. aureus, Enterococcus spp., S. pneumoniae, E. coli , K. pneumoniae , E. cloacae, P. aeruginosa , A. baumannii Following are the results: (Data from General Hospital (more than 300 beds))


Staphylococcus aureus

Medium Sized Hospital
Table * Antimicrobial resistance rates (%) of S. aureus isolated from hospitals

* Including cefoxitin, † Not tested, ‡ Trimethoprim-Sulfamethoxazole, , ∥ Quinupristin-Dalfopristin




Figure * Antimicrobial resistance rates (%) of S. aureus isolated from general hospitals


Enterococcus faecalis

Table * Antimicrobial resistance rates (%) of E. faecalis isolated from general hospitals

* Not tested

Figure * Antimicrobial resistance rates (%) of E. faecalis isolated from general hospitals


Table * Antimicrobial resistance rates (%) of E. faecium isolated from general hospitals

* Not tested, † Quinupristin-Dalfopristin

Figure * Antimicrobial resistance rates (%) of E. faecium isolated from general hospitals


Streptococcus pneumoniae

Table * Antimicrobial resistance rates (%) of S. pneumoniae isolated from general hospitals

* Not tested, † Trimethoprim-Sulfamethoxazole

Figure * Antimicrobial resistance rates (%) of S. pneumoniae isolated from general hospitals


Major Trend of Antibiotic Resistance

As shown on the above data, among gram positive bacteria, antibiotic resistance of S. pneumoniae against penicillin G increased substantially in 2010 and reduced by 5.6% in 2012. On the other hand, antibiotic resistance of gram-negative bacteria has not much changed except A. baumannii that recorded 71.1% of resistance rate in 2010 and moderately decreased to 69.5% in 2012.

Figure * Resistance trends of Gram-positive cocci isolated from general hospitals

Trend of Antibiotic Resistance Infection (Small & Medium Sized Hospitals)

Staphylococcus aureus

Medium Sized Hospital Table * Antimicrobial resistance rates (%) of S. aureus isolated from hospitals

* Including cefoxitin.
† The resistance rates were calculated from automation equipment R/I/S interpretations (upper) and MIC values (lower).
‡ Trimethoprim-Sulfamethoxazole, ∥ Quinupristin-Dalfopristin. § Vancomycin-intermediate S. aureus
(VISA) ; 2007(0.2%), 2008(0.3%), 2009(0.2%), 2010(0.1%), 2011(0.0%), 2012(0.1%).


Figure * Antimicrobial resistance rates (%) of S. aureus isolated from hospitals

Long Term Care Facility Table * Antimicrobial resistance rates (%) of S. aureus isolated from geriatric care hospitals

* Including cefoxitin. † The resistance rates were calculated from automation equipment R/I/S interpretations (upper)
and MIC values (lower). ‡ Trimethoprim-Sulfamethoxazole, ∥ Quinupristin-Dalfopristin.
§ Vancomycin-intermediate S. aureus (VISA); 2007 (0.2%), 2008 (0.3%), 2009 (0.2%), 2010 (0.1%), 2011 (0.0%), 2012(0.0%).



Figure * Antimicrobial resistance rates (%) of S. aureus isolated from geriatric care hospitals

Small Clinics Table * Antimicrobial resistance rates (%) of S. aureus isolated from clinics

* Including cefoxitin. † The resistance rates were calculated from automation equipment R/I/S interpretations (upper) and MIC values (lower).
‡ Trimethoprim-Sulfamethoxazole, ∥ Quinupristin-Dalfopristin. § Vancomycin-intermediate S. aureus
(VISA) ; 2007 (0.2%), 2008 (0.3%), 2009 (0.2%), 2010 (0.1%), 2011 (0.0%), 2012 (0.0%).

Figure * Antimicrobial resistance rates (%) of S. aureus isolated from clinics

Result

Antibiotic Resistance of MRSA against oxacillin from 2007 to 2012 showed the order of higher infection at long term care facilities, hospitals
and individual clinics. It is alarming that the infection rate of long term care facilities is around 80%.

Figure * Trends of oxacillin resistance for S. aureus by hospital type

Enterococcus faecalis


Hospitals Table * Antimicrobial resistance rates (%) of E. faecalis isolated from hospitals




Hospitals Table * The resistance rates were calculated from automation equipment R/I/S interpretations (upper) and MIC values (lower).

Hospitals Table Figure * Antimicrobial resistance rates (%) of E. faecalis isolated from hospitals

Long-term Care Facilities


Hospitals Table Table * Antimicrobial resistance rates (%) of E. faecalis isolated from geriatric care hospitals

* The resistance rates were calculated from automation equipment R/I/S interpretations (upper) and MIC values (lower).

Figure * Antimicrobial resistance rates (%) of E. faecalis isolated from geriatric care hospitals

Small Clinics Table * Antimicrobial resistance rates (%) of E. faecalis isolated from clinics

Small Clinics * The resistance rates were calculated from automation equipment R/I/S interpretations (upper) and MIC values (lower).

Small Clinics Figure * Antimicrobial resistance rates (%) of E. faecalis isolated from clinics

Enterococcus faecium

Small Clinics Hospitals Table * Antimicrobial resistance rates (%) of E. faecium isolated from hospitals

Small Clinics Hospitals * Quinupristin-Dalfopristin

Figure * Antimicrobial resistance rates (%) of E. faecium isolated from hospitals

Long-Term Care Facilities

Table * Antimicrobial resistance rates (%) of E. faecium isolated from geriatric care hospitals

* Quinupristin-Dalfopristin

Figure * Antimicrobial resistance rates (%) of E. faecium isolated from geriatric care hospitals

Small Clinics Table * Antimicrobial resistance rates (%) of E. faecium isolated from clinics

* Quinupristin-Dalfopristin



Small Clinics Figure * Antimicrobial resistance rates (%) of E. faecium isolated from clinics

Vancomycin resistance rate of VRE E. faecalis is much lower than that of E. faecium, which is less than 1.0%. Vancomycin resistance rate of E. faecium at the long-term care facilities is rapidly increasing from 20.5% in 2007, 41.7%, 2009, and 55.6% in 2012 respectively. Vancomycin resistance rate at the small clinics is 23.9% in 2012, increased more than twice from 2010, higher than that of hospitals (22.0%) Vancomycin resistance rate of all Enterococcus spp. (including E. faecalis and E. faecium) shows similar level at hospitals and clinics in 2011. However the ratio at the long-term care facility is in gradual increase, registering 23.8%.

Figure * Trends of vancomycin resistance for E. faecalis by hospital type

Figure * Trends of vancomycin resistance for E. faecium by hospital type

Figure * Trends of vancomycin resistance for Enterococcus spp by hospital type

Streptococcus pneumoniae

Hospital Table * Antimicrobial resistance rates (%) of S. pneumoniae isolated from hospitals

Hospital * Trimethoprim-Sulfamethoxazole.

Hospital Figure * Antimicrobial resistance rates (%) of S. pneumoniae isolated from hospitals

Hospital Long-term Care Facilities

Hospital Table * Antimicrobial resistance rates (%) of S. pneumoniae isolated from geriatric care hospitals

Hospital * Trimethoprim-Sulfamethoxazole.

Hospital Figure * Antimicrobial resistance rates (%) of S. pneumoniae isolated from geriatric care hospitals

Individual Clinics Table * Antimicrobial resistance rates (%) of S. pneumoniae isolated from clinics

* Trimethoprim-Sulfamethoxazole.

Figure * Antimicrobial resistance rates (%) of S. pneumoniae isolated from clinics

Analysis of the Antibiotic Resistance Depending on the Patient Type

Antibiotic resistance rates of all medical care providing institutions have shown steady decrease from 2007. In 2007, among 5373 Patients of government operating health centers 16.1% have shown antibiotic resistance and 5.5 % multi-drug resistance. Afterward, the ratios have been slightly decreased each year. Meanwhile antibiotic resistance of private health care institutions is much higher: 29.1% in 2007, 19.8% in 2008, 23.6% in 2009, 21.4% in 2010, and 18.4% in 2011 respectively.

Table * Comparison of resistance rates (%) between public health centers and hospitals

*Any Resistance (%)

Detection System in Korea

MRSA Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most severe antibiotic resistant pathogens causing hospital infection and other diseases such as purulent infection, bacteremia. The isolation ratio of MRSA is gradually increased up to 80% in the hospital, which makes a limitation for treatment of antibiotics because the isolated MRSA show resistance to methicillin as well as other antibiotics. To deal with the spread of MRSA infection, medical community as well as the government have paid acute attention on the surveillance of the infection.

Common used method for the detection of MRSA in the hospitals is Susceptibility Test. Another detection method is MecA gene by PCR, which is not commonly used in the hospitals because of the cost consideration. However mecA is known to be more accurate than Susceptibility Testing.

Standard Detection Procedure used by Hospitals in Korea

1. Taking Sample

1)Take secretion from infected skin with sterilized swap.
2)Taking phlegm from a potential patient or for those who cannot cough by themselves because of respirator, taking samples by cleansing of respiratory organ or bronchoscopy.
3) Taking urine sample from a potential patent or poley-catheter.
4) Taking blood sample.


2. Conduct susceptibility test

It usually takes 48 hours for a patient to get the result. In case
that the patient asks faster detection, other detection method
such as PCR, DNA sequencing are recommended. The
alternative test can produce the result within a few hours.

MIC (Minimum Inhibitory Concentration) is most commonly used susceptibility test. It is used for the detection of all pathogens. However, pathogens such as Streptococcus, Haemophilus, Neisseria that are hard to be cultivated are not detected by MIC. Mcroscan system that is using automated microdilution and E-test are used for MIC.

Paper Disk Method For the test, spread plate culture and pour plate culture are mostly used. Depending on the type of LB agar plate and testing antibiotics, many manufactures have been offered a variety of testing kit. This method should be done by manual procedure from the beginning to the end. Therefore standardized reliable protocols of the testing method should be developed and well observed.

Agar Dilution Method

The antibiotic to be tested is added to agar, which is then placed in dilution plates and diluted with varying levels of water. After this, the pathogen to be tested is added to each plate, plus a control plate that does not receive any antibiotics. The dilution plates are then incubated at a temperature of 37 degrees C. The plates are then incubated for sixteen to eighteen hours, although incubation time may be less for bacteria populations that divide quickly. After incubation, the plates are examined to determine if bacterial expansion has occurred. The lowest concentration of antibiotics that stopped the spread of the bacteria is considered to be the minimum inhibitory concentration of that bacteria

Agar dilution is considered to be the standard of susceptibility testing, or the most accurate way to measure the resistance of bacteria to antibiotics. The results of agar dilution are easily reproduced and they can be monitored at a much cheaper cost than what is required of other dilution methods. Additionally, up to thirty pathogen samples (plus two controls) can be tested at 0o0nce, so agar dilution is useful for batch tests.

Each dilution plate in agar testing has to be manually infected with the pathogen to be tested, so agar dilution testing is both labor intensive and expensive. And agar dilution cannot be used to test more than one pathogen at a time.

Broth Dilution Method

The tube dilution test is the standard method for determining levels of resistance to an antibiotic. Serial dilutions of the antibiotic are made in a liquid medium which is inoculated with a standardized number of organisms and incubated for a prescribed time. The lowest concentration (highest dilution) of antibiotic preventing appearance of turbidity is considered to be the minimal inhibitory concentration (MIC). At this dilution the antibiotic is bacteriostatic.

Varying concentrations of the antibiotics and the bacteria to be tested are then added to the plate. The plate is then placed into a non-CO2 incubator and heated at thirty five degrees C for sixteen to twenty hours. Following the allotted time, the plate is removed and checked for bacterial growth. If the broth became cloudy or a layer of cells formed at the bottom, then bacterial growth has occurred.

The broth dilution method can be used to test the susceptibility of bacteria to multiple antibiotics at once. Broth dilution is also highly accurate. The Other advantages include the commercial availability of plates, the ease of testing and storing the plates, and the ability for the results of some tests to be read by machines. However, the broth dilution method is only effective for testing Bacteroides fragilis. It could potentially be used with other bacteria populations, but the results would have to be correlated with agar dilution tests to be considered reliable. Although the tube dilution test is fairly precise, the test is laborious because serial dilutions of the antibiotic must be made and only one isolate can be tested in each series of dilutions.

ß-Lactamase test

Beta-Lactamase Test is a means of detecting the enzyme beta-lactamase, which confers penicillin resistance to various bacterial organisms by cleaving the beta-lactam ring of penicillin and cephalosporin antibiotics. A wide variety of bacteria produce this enzyme, including both gram-positive and gram-negative organisms. This acidimetric method is recommended for use in testing beta-lactamase production by Neisseria gonorrhoeae, Haemophilus species and Staphylococcus species.

E-Test

Etest, (previously known as Epsilometer test) manufactured by bioMérieux, is a manual in vitro diagnostic device used by laboratories to determine the MIC and whether or not a specific strain of bacterium or fungus is susceptible to the action of a specific antimicrobial. This type of test is most commonly used in healthcare settings to help guiding physicians in treatment of patients by indicating what concentration of antimicrobial successfully would treat the infection.
MIC test has been used as standard test method of the detection of antibiotic resistance in hospitals. It has weaknesses such frequent error caused by agar LB, disk, tested pathogens, reference strain, and cultivation condition, and lab technician.

Another shortcoming of MIC test is the time to get the result. In terms of accuracy and required time, other advanced tests such as mecA PCR Method is recommended by some hospitals. But still majority of detection is being by MIC.

3. Cost of the Detection

Actual cost needed for the detection varies hospitals from hospitals. However average cost of susceptibility test is 55000KW ($50) to 90000KW ($85). For other test, the testing cost is more than 250000KW ($ 200). Testing expense is not covered by mandatory government insurance plan. Thus, if the patient does not have private insurance policy, she should pay by herself.

US

The CDC reported that each year in the United States only, at least 2 million people acquire serious infections with bacteria that are resistant to one or more antibiotics designed to treat the very infection. At least 23,000 people die each year as a direct result of these antibiotic-resistant infections. Many more die from other medical conditions that were further complicated by an antibiotic-resistant infection. (Source: Antibiotic Resistant Threats in the United States 2013, Center for Disease Control and Prevention)

In order to cope with the threats, CDC is adopted five major tasks in order to support initiatives of the White House’s National Strategy to Combat Antibiotic Resistant Bacteria (https://www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf)and the President’s Executive Order(https://www.whitehouse.gov/the-press-office/2014/09/18/executive-order-combating-antibiotic-resistant-bacteria)

Slow the Development of Resistant Bacteria and Prevent the Spread of Resistant Infections
Strengthen National One-Health Surveillance Efforts to Combat Resistance
Advance Development and Use of Rapid and Innovative Diagnostic Tests for Identification and Characterization of Resistant Bacteria
Accelerate Basic and Applied Research and Development for New Antibiotics, Other Therapeutics, and Vaccines
Improve International Collaboration and Capacities for Antibiotic Resistance Prevention, Surveillance, Control, and Antibiotic Research and Development

In order to fully implement the National Strategy for Combating Antibiotic-Resistant Bacteria, the FY16 AR Solution Initiative was adopted. This implementation will include: comprehensive tracking and detection of antibiotic-resistant bacteria, faster outbreak response, insights for research innovation, better patient care, improved prescribing, increased susceptibility testing, nationwide implementation of CDC’s Core Elements of Hospital Antibiotic Stewardship (http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html), and global partnerships for prevention and detection.

The FY16 budget also supports a $14 million increase for the National Healthcare Safety Network (NHSN)—the nation’s leading system to track healthcare-associated infections, including antibiotic resistance and antibiotic use—as a companion to CDC’s FY16 Antibiotic Resistance Solutions Initiative, supporting multiple goals under the National Strategy, including new activities to better understand and monitor sepsis, leading to enhanced prevention to save lives.

One of the elements of the initiative is advance development and use of rapid and innovative diagnostic tests for identification and characterization of resistant bacteria. FY 16 AR Solution initiative also includes comprehensive tracking and detection of antibiotic-resistant bacteria.

According to the National Action Plan to Combat Antibiotic-Resistant Bacteria released on 27, March, 2015, Improved detection and control of antibiotic resistance in human and animal pathogens will be achieved through a “One-Health” approach to disease surveillance that integrates data from multiple monitoring networks. To achieve the goal by 2020 the government has adopted action plan in order to generate significant outcomes.

Action Plan

Creation of a regional public health network—the Detect Network of AR Regional Laboratories—for resistance testing, a specimen repository for resistant bacterial strains, and a National Sequence Database of Resistant Pathogens.

Routine reporting of antibiotic use and resistance data to National Health Safety Network (NHSN) by 95% of Medicare-eligible hospitals, as well as by Department of Defense and Veterans Affairs healthcare facilities.

Routine testing of zoonotic and animal pathogens for antibiotic susceptibility at ten to twenty National Animal Health Laboratory Network (NAHLN) and Veterinary Laboratory Investigation and Response Network (Vet-LIRN) member laboratories, using standardized testing methods and data sharing practices.

Also important is advance development and use of rapid and innovative diagnostic tests for identification and characterization of resistant bacteria. In order to facilitate the achievement of the task, the government will take the lead with the support of funding agencies such as the National Institutes of Health. When it is achieved researchers are taking advantage of new technologies to develop rapid “point-of-need” diagnostic tests that can be used during a healthcare visit to distinguish between viral and bacterial infections and identify bacterial drug susceptibilities — an innovation that could significantly reduce unnecessary antibiotic use. The availability of new rapid diagnostic tests, combined with ongoing use of culture-based assays to identify new resistance mechanisms, will advance the detection and control of resistant bacteria.

By 2020, significant outcomes in this area will include:

Development and dissemination of authorized point-of-need diagnostic tests that rapidly distinguish between bacterial and viral infections.

Validation of diagnostic tests that rapidly determine the antibiotic resistance profiles of bacteria of public health concern.

As proved by these efforts, it is critical to detect antibiotic resistant bacteria as early as possible and eventually to develop “point-of-need” diagnostic test. Our project is to contribute to the early detection of antibiotic resistant bacteria by using quorum sensing. We have succeeded to create plasmids to detect antibiotic resistant bacteria though we are aware that it is rudimentary development of such kind but we believe it is used as a proof of concept and with advanced research efforts, it can be further developed to an extent that it can be used at the health care institutions and nursing homes. Our hope is to develop a simple kit just like diabetic test kit, so that anyone who needs detection of antibiotic resistance can use it.

Current detection methods require complicated procedure. As described in our background of project.(https://2015.igem.org/Team:elan_vital_korea/background#) Consequently, Antibiotic-resistant infections add considerable costs to the US healthcare system that can be avoided by devising ways to diagnose and treat those infections. Generally, patients suffering from antibiotic-resistant infections require prolonged, more expensive treatments, stay at hospitals longer, demand additional doctor visits, attention and care, and result in greater disability and death than those who were infected but can be easily treated using antibiotics. The total economic cost of antibiotic-resistance to the US economy is difficult to calculate, but is estimated to be as high as $20 billion of direct healthcare costs, plus additional burden to society for lost productivity of about $35 billion a year. (source: CDC). Unfortunately, information on unit cost for detecting antibiotic resistant bacteria is not available. We have tried to search the website of 100 largest hospitals in the U.S and called 50, but got responded by hospitals that they cannot release exact cost which may vary case by case.

Observations

It is urgent to develop easy and quick detection method given the significance of risks posed by antibiotic resistant pathogens. Research on the current status of containment strategies in the US and Korea make us reaffirmed that our project is worthwhile efforts to be pursued enthusiastically. Our team at Elan Vital Korea is drawn by the idea that we may be able to rapidly and efficiently detect infection by antibiotics-resistant bacteria using a synthetic biology methodology, quorum sensing (QS).

Reference

The White House, NATIONAL STRATEGY FOR COMBATING ANTIBIOTICRESISTANT BACTERIA, NATIONAL STRATEGY FOR COMBATING ANTIBIOTICRESISTANT BACTERIA

The White House, Executive Order -- Combating Antibiotic-Resistant Bacteria

Center for Disease Control and Prevention http://www.cdc.gov/

Korean Center for Disease Control and Prevention (http://www.cdc.go.kr/search/sEngine.jsp?kwd=MRSA%EA%B0%90%EC%97%BC_

Korea Antibiotic Resistance Monitoring System,(KARMS), Annual Report, 2009, 2011, Korea CDC, NIH
http://www.ncbi.nlm.nih.gov/pubmed/21140281

Hye Soo Lee, Hyun Lim, Evaluation of Various Methods for Detection of Methicillin Resistance Staphylococcus aureus (MRSA), Department of Laboratory Medicine, Chonbuk National University Medical School, and Institute for Medical Sciences, Chonju, Korea

Soo Jung Kim, Comparison Between Antimicrobial Susceptibility Test and mecA PCR Method for Reading of Methicillin-Resistant Staphylococcus aureus, Korea Journal of Microbiology, Vol. 47, 2011.12, p381-p385

Eun-Sung Moon , Paper Disc Method, MIC Test, CNU Biochemistry Lab.

R. STALONS and CLYDE THORNSBERRY , Broth-Dilution Method for Determining the Antibiotic Susceptibility of Anaerobic Bacteria Department of Microbiology, Health Sciences Center, Temple. University, Philadelphia, Pennsylvania 19140; and Antimicrobics Investigation Section, Center for Disease Control, Atlanta, Georgia 30333

Kyung Lee, Se Ran Heo, Soon He Choi, Sang Hoon Song, Kyoung Un Park, Junghan Song, and Eui Chong Kim, Comparison of Various Methods for Detection of Methicillin-Resistant Staphylococcus aureus Department of Laboratory Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Korea Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea

Jongyoun Yi, Eui-Chong Kim Microbiological Characteristics of Methicillin-resistant Staphylococcus aureus 1 Department of Laboratory Medicine, Seoul National University Hospital, 2 Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea

Hong-Bin Kim, Chong Moon Sa, Jaeil Yoo, Bong Su Kim, Ok Jin Yun , Hye Ryoung Yoon and Yeong Seon Lee, Antibiotic Resistance Patterns of Staphylococcus aureus Isolated from the Patients Admitted to Non-tertiary Hospitals Laboratory of Nosocomial Pathogens, Department of Microbiology, National Institute of Health (NIH) and Seoul Clinical Laboratories (SCL)* , Seoul, Korea

Kwon, Young-Il, Tae-Woon Kim , Hae-Yeong Kim , Yun Hee Chang , Hyo-Sun Kwak , Gun-Jo Woo , and Yun-Hee Chung,Monitoring of Methicillin Resistant Staphylococcus aureus from Medical Environment in Korea. Test and Research Center, Korea Consumer Protection Board, Seoul 137-700, 1 Institute of Life Sciences & Resources, Kyung Hee University, Suwon 449-701, Korea, 2 Department of Food and Nutrition, Myongji University, Yongin 449-728, Korea, 3 Center for Food Safety Evaluation, Korea Food and Drug Administration, Seoul 122-704, Korea

Mayo Clinic www.mayoclinic.org/

Massachusetts General Hospital www.massgeneral.org/

Cleveland Clinic http://my.clevelandclinic.org/

UCSF Medical Center www.ucsfhealth.org/



Johns Hopkins Hospital http://www.hopkinsmedicine.org/the_johns_hopkins_hospital/

New York-Presbyterian University Hospital of Columbia and Cornell http://www.newyorkpresbyterianhospital.com/

Northwestern Memorial Hospital http://www.nm.org/location/northwestern-memorial-hospital

Yale-New Haven Hospital www.ynhh.org/

Asan Medical Center http://www.amc.seoul.kr/asan/main.do

Samsung Medical Center http://www.samsunghospital.com/home/main/index.do

Seoul National University Hospital http://www.snuh.org/

Severance Hospital http://sev.iseverance.com/

The Catholic University Korea Seoul Saint Mary’s Hospital http://www.cmcseoul.or.kr/

Gachon University Kil Medical Center http://www.gilhospital.com/

Korea University Medical Center http://www.kumc.or.kr/main/index.do

Ajou University Hospital http://hosp.ajoumc.or.kr/

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Education & Public Awareness: Korea Youth Expo

Elan Vital Korea’s education and public awareness-related human practice efforts – that is, our human practice efforts that are not directly related to our project at hand: using quorum sensing technology for early, efficient detection of MRSA or other antibiotics-resistant bacteria – focus primarily on our outreach at the Korea Youth Expo(http://www.youthexpo.kr/) this May.


EDUCATION & PUBLIC AWARENESS

Threats of Antibiotics-Resistant Bacteria

For this purpose, Elan Vital Korea has set up a synthetic biology research club jointly with YMCA, which participated in the Korea Youth Expoas a program provider. The selection criteria for the provider was very high, and competition fierce. Ultimately, however, the hard work and preparation has been amply rewarded when the club was selected as one of 100 teams from more than 2,500 schools and community organizations. Korea Youth Expo is as the largest, most significant annual event for the young generation since its inception in 2001. The annual event is organized by the Ministry of Gender Equality and Family of Korea, and run by Korea Youth Work Agency. This year, Korea Youth Expo was held in Gumi, Korea from 21st to 23rd, May. For the three days, about 159,600 people visited the event. We did our best to fully exploit the opportunity and promote the ideas of synthetic biology, bio-safety and bio-ethics. Our activities at the Expo are: (1) preparation meetings, (2) on-booth experiment sessions and DNA-related activities, (3) information seminar on synthetic biology, (4) on-booth discussions and talks on synthetic biology, and (5) survey.


1. Preparation Meetings

We held more than a dozen preparation meetings.





2. On-booth Experiment Sessions and DNA-Related Activities

For 3 days, we taught more than 500 visitors about conducting DNA extraction experiments and assembling DNA models.

(1) Broccoli DNA Extraction Experiment

We have explained the DNA structure while students were conducting the experiments. Following pictures had been used to make visitors understand better.

1. Grind broccoli using the blender.
2. For 25g of broccoli, put 2g of salt and 7g of surfactant (liquid detergent) into 150ml of distilled water, then stir until it is completed melted, and wait for 5-10 minutes. The detergent captures the proteins and liquids of the cell membranes.

3. Pour the grinded broccoli through a strainer into another container.
4. Pour the mixture into test tubes (or small glass containers).

5. Tilt the test tube and slowly pour rubbing alcohol (70-95% isopropyl or ethyl
alcohol) into the tube down the side so that it forms a layer of the broccoli mixture.
6. DNA will rise into the alcohol layer from the broccoli layer. Use a glass stirring rod (or wooden stick) to draw the DNA into the alcohol.




3. Information Seminar on Synthetic Biology


Elan Vital Korea has organized an information seminar on synthetic biology during the Korea Youth Expo. For the seminar, we have invited Mr. Damon Tighe as our lecturer, who conducted the lecture in the English language, which was simultaneously translated into the Korean language. We have invited college students and professors as well as high school students visiting the expo. We also held an introduction session on iGEM. The entire session was video recorded, and offered to various institutions.





4. On-Booth Discussions and Talks on Synthetic Biology


We explained to the visitors of our booth what is the synthetic biology, and what benefits and risks are inherent in the new field full of great potential and possibility. We began our discussions with visitors of our booth by asking them to express their opinions on the synthetic biology. This way, we were able to customize the level of information we share based on their answers and feedbacks. In the process of the discussions, we showed them various displays, including various pictures, videos, information brochures and the glow fish on display in our booth to explain the synthetic biology.




5. Survey


Click here to see the Questionnaire

We have conducted surveys by designing questionnaires, distributing them to the visitors to our booth, then gathering their responses. The questionnaire is designed to solicit information on the level of public awareness of the topics and issues related to the synthetic biology. The survey results, which are summarized below, will give us better understanding of the public awareness of the synthetic biology and tools to better plan our promotional, human practice activities in the future.

Most of the respondents belong to the age group of 10-18 years old. In fact, more than 80% of respondents belong to that age group. The result is expected, considering that the survey was conducted at the Youth Expo. Male respondents are tree times larger than female. The largest age group is high school students, followed by under and over graduates. Since program providers are mostly high school and college club members, the result is expected.

B. Public Awareness of Synthetic Biology

In general, the younger the respondent is, less likely that they knew what the synthetic biology meant, or ever heard about it. Respondents aged between 10 and 15, 174 out of 222 (about 78.83%) answered that they have never heard of the synthetic biology. Respondents belonging to the age group 16-18 showed similar results: 75% (147 out of 196) have never been exposed to the definition of the synthetic biology. As ages increase, more people answered that they have at least heard about it, or know what it is. About 66.67% of people aged between 19 and 25 (52 out of 78) responded that they have heard about the synthetic biology. For older age groups, more than 55% of age group between 26 and 40 and 83% of age group between 41 and 50 respectively understood what synthetic biology means. The result, however, is not reliable because the total number of sample belonging to these age groups are very few (only 15 out of 511). Furthermore, that they are aware of the subject is rather expected, considering that they visited the Youth Expo at all, visited our booth and volunteered to participate in the survey. The results seem to suggest that the synthetic biology is not well understood or accepted among school age teenagers.




Comparing the result we got with the results obtained by the Team Oxford in 2014 iGEM and and UCL London 2010 (see the charts above), general public in Korean including high school and college students show higher percentage of people who have been informed of and/or interested in synthetic biology.

But comparing the results with those obtained in Hong Kong, Korea’s Asian neighbor, the level of public awareness of the synthetic biology among Korean population are substantially lower than residents of Hong Kong. It is rather surprising considering that the Korean government has demonstrated that it has a strong desire to drive growth in the synthetic biology-related industries. In August 2011, the Korean government has selected the synthetic biology as one of the ‘Global Frontier Businesses’ and established the Intelligent Synthetic Biology Center later the same year, in order to support the research and business development in the field. The Center (including 11 universities and more than 200 researchers) leads the development of the synthetic biology in Korea. In short, the government’s strong drive for the synthetic biology did not result in heightened public awareness of the field. The observation is supported by the level of participation in iGEM, which is quite low compared to the government’s and the industry’s drive and efforts to make the industry thriving. The result seem to suggest that as a further study, we need to look deeper into the actual works performed by the government, academics and the industry to promote the synthetic biology, and identify the challenges and issues that hinder the development of the synthetic biology despite government’s and industry’s resolution and drive.



c. Public Attitude Toward Specific Area of Synthetic Biology/Genetic Engineering

Answers on Question 5 shows interesting observation: The phrase we use to solicit answer leads to extremely different responses. Respondents expressed their concerns and generally responded negatively if the question includes the phrase “gene modification, gene alteration, etc.,” but answered more positively if the question is about the “genetic engineering.” The contrasting results seem to suggest that people do not understand what genetic engineering means, or what kind of works are done in the field. Also, people were more understanding and forgiving if given more generic, comprehensive phrases such as “genetic engineering” rather than specific works such as “gene modification or alteration.” The result also seems to show that the public attitude is largely decided based on the particular phrase used, (verbal and nonverbal) nuances and cultural contexts in which the phrase appears.

Absolute majority of respondents (about 65%) thought that the genetic engineering should be permitted only when justified by clear reasons and right purposes. About 17% said that the genetic engineering is very dangerous, and prohibited at any cost. About 10% answered that the genetic engineering should be permitted, even though it may pose dangers and concerns. And, another 9% of the respondents thought that the genetic engineering should be allowed for the welfare of the humanity.


About 10% answered that the genetic engineering should be permitted, even though it may pose dangers and concerns. And, another 9% of the respondents thought that the genetic engineering should be allowed for the welfare of the humanity.




6. Follow-up Activities at the Korea Science Festival
Click here to see the Questionnaire

As follow-up activities, we have supported a few science clubs that are selected program roviders at the Korea Science Festival held from 27th of July to 3rd of August. We were not eligible for operating a booth at the event, because Elan Vital Korea is not a school science club but an interschool club comprising different school students. We had conducted subsequent survey for 141 program providers. Our initial expectation was that they must have had interests and knowledge on the synthetic biology, as they are members of science clubs in schools. However, the result showed otherwise.


Concerns About Synthetic Biology

Comparing the result we obtained with similar survey results obtained in the US and EU (UK), we observed that the public attitude toward the synthetic biology shows very similar distribution. The majority believes that the level of benefit and risk of the new field are approximately equal. The result may suggest that they know about the synthetic biology, are aware of the potential risks it may have, but are not – yet – decided on whether it will benefit more, or harm more the humanity. The result supports our conclusion that we have to pay more attention on the ethics, legal and philosophical aspect of the synthetic biology.

When asked what comes to their mind first about the danger of the synthetic biology and gene modification, many respondents did not articulate their answers, but substantial portion of people (about 20-30 percent) answered the danger of human as well as animal cloning.

Comparing the responses we got with the responses of US, it seems that the Korean people do nothave sufficient knowledge on how the synthetic biology is actually used. It is possible such result is due to the fact we conducted our survey for mostly younger generations (aged between 10 and 25).


7. Observations

During the process of our education and public awareness-related human practice at Korea Youth Expo and the Korea Science Fair, we have become keenly aware of the need for educating students and young generation about the synthetic biology. As our survey result and our on-site interview show, very few youngsters knew about synthetic biology, and none heard about iGEM before. Against the background, we have adopted a few strategies to facilitate our efforts to educate general public particularly focusing on younger generation about synthetic biology and iGEM. First, we have decided to establish an extensive network with teachers and education institutions in the field. After searching multiple options and reaching out possibilities, we were able to establish a cooperative network with the National Association for Science Teachers(http://k-sta.or.kr/), a nonprofit organization established in March 2003 with the purpose of encouraging science teachers of primary and secondary institutions to enhance expertise in the cutting edge technology and of motivating them to provide better science education. We have sent our information brochure, DNA extraction experiment equipment and videos that can be used for the science teacher to work with their students in the field. We have created Youtube videos explaining synthetic biology and MRSA, which was the starting point of our project and still has urgent need to teach school aged children what is MRSA and how to protect themselves from getting infected by the antibiotics-resistant bacteria. In addition, We have decided to make public our blog which had been used by only internally to store data and resources until then. Our homepage www.elanvitalkorea.com is under construction and will be finalized mid November. We have committed to provide basic education on synthetic biology whenever requested. We believe that making full use of existing network of YMCA would be very much beneficial to promote public awareness initiative, because YMCA has extensive network comprising all ages from high school students to senior citizens. Our role there is to provide information including brochures and video and, if requested, to visit nursing homes and long term care centers for senior citizens to inform them of the dangers of antibiotics-resistance and of the measure that should be taken to reduce the infection.




8. Video on Danger of MRSA





9. Introduction to Synthetic Biology


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