Zeitschriftenartikel zum Thema „United States. Biotechnology, Biologics, and Environmental Protection“

The past decade has seen many new developments impacting the intellectual property system. The introduction of big data analytics has transformed the fields of biotechnology and bioinformatics while ushering in major advances in drug development, clinical practices, and medical financing. The arrival of biologics and personalized medicines has also revolutionized the healthcare and pharmaceutical industries. In addition, the emergence of bilateral, regional, and plurilateral trade agreements have raised serious, and at times difficult, questions concerning the evolution of domestic and international intellectual property standards. One topic linking all three developments together concerns the establishment of international standards to protect clinical trial data that have been submitted to regulatory authorities for the marketing approval of pharmaceutical products. During the negotiations for the Trans-Pacific Partnership (TPP), for example, the protection of clinical trial data submitted for the marketing approval of biologics was highly contentious. Although the United States’ withdrawal in January 2017 has since placed the TPP Agreement and its data exclusivity provisions for pharmaceuticals and biologics on life support, the debate on the protection of clinical trial data will continue and will emerge in future bilateral, regional, and plurilateral trade negotiations, including the renegotiations on the North American Free Trade Agreement (NAFTA). Part I of this Article reviews the protection of clinical trial data under Article 39.3 of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement) of the World Trade Organization (WTO). Even though the provision covers both pharmaceutical and agricultural chemical products, this Article focuses only on the former. Part II examines the additional protection clinical trial data have received through TRIPS-plus bilateral, regional, and plurilateral trade agreements. Part III outlines five specific recommendations to help advance the debate on such protection in the age of big data, biologics, and plurilateral trade agreements.

Ten years after the enactment of the Biologics Price Competition and Innovation Act (BPCIA), competition in biologics markets remains scant and far from sufficient for lowering prices of biologics to the level of 80-90% price drops seen in generic drug markets. This reality is not a result of one or two cardinal reasons, but many. If lowering the price of biologics is the goal and competition is the means by which we seek to achieve that goal, then there does not seem to be a quick fix to address all of the many impediments to competition that plague biologics markets. Yet, certain changes to how the Food and Drug Administration (FDA) evaluates and approves biologics may go a long way toward the creation of meaningful competition in biologics markets. One such change would be making original biologics' manufacturing information available to follow-on manufacturers.As recognized by several commentators, access to biologics manufacturing information is key to increasing competition in biologics markets. Without access to such information, making follow-on biologics is difficult and expensive, if not outright impossible. This is expected to be especially true for the highly anticipated class of interchangeable biologics, none of which has been approved by the FDA to date. Yet, it has long been the position of the brand-name pharmaceutical industry (Industry) that biologics manufacturing information is proprietary and, thus, may not be shared. Congress has subscribed to the Industry's position, prohibiting the FDA from disclosing regulatory filings submitted by developers of original biologics, including manufacturing information, to third parties. That prohibition not only undermines competition in biologics markets, but is also wasteful, potentially unethical, and poses unnecessary risks to the health and safety of patients.This article makes the case for FDA sharing of original biologics manufacturing information with follow-on biologics developers. It is informed by the similar legal and commercial circumstances in the area of pesticides and the regulatory regime established by Congress in the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), which is administered by the Environmental Protection Agency (EPA). The article reviews the FIFRA regime, including its upholding as constitutional by the United States Supreme Court, and then examines its applicability to the area of biologics. The article concludes with a proposal for a similar regime to be incorporated into the pathway for approval of follow-on biologics as a means of increasing competition in biologics markets.

ABSTRACT Collaborative and in-house laboratory trials were conducted to evaluate Cryptosporidium oocyst and Giardia cyst recoveries from source and finished-water samples by utilizing the Filta-Max system and U.S. Environmental Protection Agency (EPA) methods 1622 and 1623. Collaborative trials with the Filta-Max system were conducted in accordance with manufacturer protocols for sample collection and processing. The mean oocyst recovery from seeded, filtered tap water was 48.4% ± 11.8%, while the mean cyst recovery was 57.1% ± 10.9%. Recovery percentages from raw source water samples ranged from 19.5 to 54.5% for oocysts and from 46.7 to 70.0% for cysts. When modifications were made in the elution and concentration steps to streamline the Filta-Max procedure, the mean percentages of recovery from filtered tap water were 40.2% ± 16.3% for oocysts and 49.4% ± 12.3% for cysts by the modified procedures, while matrix spike oocyst recovery percentages ranged from 2.1 to 36.5% and cyst recovery percentages ranged from 22.7 to 68.3%. Blinded matrix spike samples were analyzed quarterly as part of voluntary participation in the U.S. EPA protozoan performance evaluation program. A total of 15 blind samples were analyzed by using the Filta-Max system. The mean oocyst recovery percentages was 50.2% ± 13.8%, while the mean cyst recovery percentages was 41.2% ± 9.9%. As part of the quality assurance objectives of methods 1622 and 1623, reagent water samples were seeded with a predetermined number of Cryptosporidium oocysts and Giardia cysts. Mean recovery percentages of 45.4% ± 11.1% and 61.3% ± 3.8% were obtained for Cryptosporidium oocysts and Giardia cysts, respectively. These studies demonstrated that the Filta-Max system meets the acceptance criteria described in U.S. EPA methods 1622 and 1623.

ABSTRACT Analyses for the presence of indicator organisms provide information on the microbiological quality of water. Indicator organisms recommended by the United States Environmental Protection Agency for monitoring the microbiological quality of water include Escherichia coli, a thermotolerant coliform found in the feces of warm-blooded animals. These bacteria can also be isolated from environmental sources such as the recreational and pristine waters of tropical rain forests in the absence of fecal contamination. In the present study, E. coli isolates were compared to E. coli K12 (ATCC 29425) by restriction fragment length polymorphism using pulsed-field gel electrophoresis. Theoretically, genomic DNA patterns generated by PFGE are highly specific for the different isolates of an organism and can be used to identify variability between environmental and fecal isolates. Our results indicate a different band pattern for almost every one of the E. coli isolates analyzed. Cluster analysis did not show any relations between isolates and their source of origin. Only the discriminant function analysis grouped the samples with the source of origin. The discrepancy observed between the cluster analysis and discriminant function analysis relies on their mathematical basis. Our validation analyses indicate the presence of an artifact (i.e., grouping of environmental versus fecal samples as a product of the statistical analyses used and not as a result of separation in terms of source of origin) in the classification results; therefore, the large genetic heterogeneity observed in these E. coli populations makes the grouping of isolates by source rather difficult, if not impossible.

ABSTRACT Ct values, the concentration of free chlorine multiplied by time of contact with virus, were determined for free-chlorine inactivation experiments carried out with chloroform-extracted (dispersed) and non-chloroform-extracted (aggregated) feline calicivirus (FCV), adenovirus type 40 (AD40), and polio virus type 1 (PV-1). Experiments were carried out with high and low pH and temperature conditions. Ct values were calculated directly from bench-scale free-chlorine inactivation experiments and from application of the efficiency factor Hom model. For each experimental condition, Ct values were higher at pH 8 than at pH 6, higher at 5°C than at 15°C, and higher for dispersed AD40 (dAD40) than for dispersed FCV (dFCV). dFCV and dAD40 were more sensitive to free chlorine than dispersed PV-1 (dPV-1). Cts for 2 log inactivation of aggregated FCV (aFCV) and aggregated PV-1 (aPV-1) were 31.0 and 2.8 orders of magnitude higher than those calculated from experiments carried out with dispersed virus. Cts for 2 log inactivation of dFCV and dAD40 in treated groundwater at 15°C were 1.2 and 13.7 times greater than in buffered-demand-free (BDF) water experiments at 5°C. Ct values listed in the U.S. Environmental Protection Agency (EPA) Guidance Manual were close to, or lower than, Ct values generated for experiments conducted with dispersed and aggregated viruses suspended in BDF water and for dispersed viruses suspended in treated groundwater. Since the state of viruses in water is most likely to be aggregated and associated with organic or inorganic matter, reevaluation of the EPA Guidance Manual Ct values is necessary, since they would not be useful for ensuring inactivation of viruses in these states. Under the tested conditions, dAD40, dFCV, aFCV, dPV-1, and aPV-1 particles would be inactivated by commonly used free chlorine concentrations (1 mg/liter) and contact times (60 to 237 min) applied for drinking water treatment in the United States.

ABSTRACT Although it is recognized that acidification of freshwater systems results in decreased overall species richness of plants and animals, little is known about the response of aquatic microbial communities to acidification. In this study we examined bacterioplankton community diversity and structure in 18 lakes located in the Adirondack Park (in the state of New York in the United States) that were affected to various degrees by acidic deposition and assessed correlations with 31 physical and chemical parameters. The pH of these lakes ranged from 4.9 to 7.8. These studies were conducted as a component of the Adirondack Effects Assessment Program supported by the U.S. Environmental Protection Agency. Thirty-one independent 16S rRNA gene libraries consisting of 2,135 clones were constructed from epilimnion and hypolimnion water samples. Bacterioplankton community composition was determined by sequencing and amplified ribosomal DNA restriction analysis of the clone libraries. Nineteen bacterial classes representing 95 subclasses were observed, but clone libraries were dominated by representatives of the Actinobacteria and Betaproteobacteria classes. Although the diversity and richness of bacterioplankton communities were positively correlated with pH, the overall community composition assessed by principal component analysis was not. The strongest correlations were observed between bacterioplankton communities and lake depth, hydraulic retention time, dissolved inorganic carbon, and nonlabile monomeric aluminum concentrations. While there was not an overall correlation between bacterioplankton community structure and pH, several bacterial classes, including the Alphaproteobacteria, were directly correlated with acidity. These results indicate that unlike more identifiable correlations between acidity and species richness for higher trophic levels, controls on bacterioplankton community structure are likely more complex, involving both direct and indirect processes.

We have successfully designed a uranyl ion (U(VI)-specific peptide and used it in the fabrication of an electrochemical sensor. The 12-amino acid peptide sequence, (n) DKDGDGYIpTAAE (c), originates from calmodulin, a Ca(II)-binding protein, and contains a phosphothreonine that enhances the sequence’s affinity for U(VI) over Ca(II). The sensing mechanism of this U(VI) sensor is similar to other electrochemical peptide-based sensors, which relies on the change in the flexibility of the peptide probe upon interacting with the target. The sensor was systematically characterized using alternating current voltammetry (ACV) and cyclic voltammetry. Its limit of detection was 50 nM, which is lower than the United States Environmental Protection Agency maximum contaminant level for uranium. The signal saturation time was ~40 min. In addition, it showed minimal cross-reactivity when tested against nine different metal ions, including Ca(II), Mg(II), Pb(II), Hg(II), Cu(II), Fe(II), Zn(II), Cd(II), and Cr(VI). Its reusability and ability to function in diluted aquifer and drinking water samples were further confirmed and validated. The response of the sensor fabricated with the same peptide sequence but with a nonphosphorylated threonine was also analyzed, substantiating the positive effects of threonine phosphorylation on U(VI) binding. This study places emphasis on strategic utilization of non-standard amino acids in the design of metal ion-chelating peptides, which will further diversify the types of peptide recognition elements available for metal ion sensing applications.

Wastewater streams contain organic molecules that need to be removal before disposal which requires an energy input on average of 6 kWh ton-1. (1) The fermentation of biomass to produce biogas employs living organisms and permits the valorization of the waste with generation of electricity. However, this technology present limitations in terms of capital cost (ranging USD0.06 and USD0.30 as a function of the size of the digester) and large volume footprint. (2) Microbial fuel cells (MFCs) offer the ability significantly reducing the Chemical Oxygen Demand (COD) contamination is waste water effluents while produce moderate amounts of power. (3) In this contribution, we present the first abiotic waste water fuel cell, a system that directly converts organic materials found in waste sources from different industries into electrical energy. The implementation of inorganic catalysts permits a so-called zero gap design which contributes to minimize the distance between the anode and cathode which is normally large for MFCs to minimize oxygen crossover. This configuration was combined with a commercial PtRu oxidation catalysts produced an unprecedented high power density when using real waste water streams (2.6 mW cm-2). Moreover, when operated in a continuous loop COD removals as high as 50% has been achieved. This abiotic system significantly reduces processing time associated to incubation periods which are necessary for bio-processes such as biogas generation. (4) References: (1) United States Environmental Protection Agency, Local Government Climate and Energy Strategy Series (2008). (2) Weiland et al., Applied Microbiology and Biotechnology 85, 849-860 (2010). (3) Liu et al., Environmental Science & Technology 38, 4040-4046 (2004). (4) Mao et al., Renewable & Sustainable Energy Reviews 45, 540-555 (2015).

A retrospective analysis of data concerned with the regulation of the transport of animals for caged animal feeding operations (feedlots) and the availability and use of antibiotics was accomplished from data available from an aggregation of domestic and global agencies. Agency data sources included are the United States Department of Agriculture‐Animal Plant Health Inspection System (USDA‐APHIS), the Environmental Protection Agency (EPA), the United States Geological Survey (USGS), Center for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), Customs and Border Protection‐Eagle Pass Sector (CBP), Drug Enforcement Administration (DEA), Texas Water Development Board‐Laredo, Texas, (TWDB), Texas Commission on Environmental Quality‐Laredo, Texas, (TCEQ), Organization for Economic Cooperation and Development (OECD), Asia Pacific Economic Cooperation (APEC), European Centre for Disease Prevention and Control (ECDC), European Medicines Agency (EMEA), Food and Agriculture Organization (FAO), World Organization for Animal Health (OIE), Transatlantic Taskforce on Antimicrobial Resistance (TATFAR), World Health Organization (WHO), and Central Drugs Standard Control Organization (CDSCO). Based on the analysis, an action plan is proposed for the Global Union for Antibiotics Research and Development[1][2][3](GUARD) to mitigate AR pandemic (ARP). The primary suggestion is the immediate establishment of a centralized database that will serve as an open‐ended system for reporting, monitoring and control, education, and information sharing in the following processes: i. Antibiotics prescription details by name of disease and dosage, ii. Amount of antibiotics produced per country and per capita, including utilization of antibiotics per country and per capita. Implementation of antibiotics time out (ATO), iii. Detection of active pharmaceutical ingredients (API) in soil and water, iv. Streamlining of the disposal of antibiotics by universal and global disposal standards (Best Available Techniques), v. Maintain a global monitoring system for emergence of AR pathogen induced infectious diseases on twenty‐four‐hour and seven day cycles, vi. Mandatory cyclic reporting (quarterly, semiannual, and annual) regarding morbidity and mortality rates due to AR pathogens, vii. Mandatory annual summit to address threats of emergence and spread of AR infectious diseases, viii. Generate global trust fund to create resources for mitigation of the AR, ix. Global implementation‐success rate of Antibiotics Timeout (ATO), x. Creation of a Pharmaco‐Ecotoxicology data sheet for “Bioaccumulation potential of antibiotics, its active pharmaceutical ingredients (API) in the non‐target organisms (aquatic, terrestrial, avian species) and Environmental risk assessment for biological response using multi‐biomarker approach. Taken together, a collective effort addressing the aforesaid suggestions on a global scale would plausibly mitigate ARP. Data analysis and adequate literature sources will be presented at EB 2017.Support or Funding InformationProfessional development funds to Subburaj Kannan

Before pesticides can be sold in the United States, the United States Environmental Protection Agency (EPA) must evaluate them thoroughly to ensure that they meet U.S. federal pesticide registration standards for human health and the environment. EPA considers pesticidal substances produced and used in plants as pesticides and defined them in the regulations as “plant-incorporated protectants” (PIPs). PIPs that are created through conventional breeding are exempted from registration requirements, while those created through biotechnology require individual assessments and approval by EPA before they can be distributed or used. This currently includes PIPs that are identical to those that could be moved through conventional breeding but are created through biotechnology (e.g., through genome editing or via precision breeding techniques). EPA proposed an exemption in October 2020 to allow certain PIPs created through biotechnology to be exempt from EPA requirements for pesticides where those PIPs: 1) pose no greater risk than PIPs that EPA has already exempted, and 2) could have otherwise been created through conventional breeding.

USDA and DHHS excluded sustainability as a topic for consideration in developing the 2015 Dietary Guidelines for Americans, contrary to recommendations by an expert advisory committee. While significant progress has been made in Europe and elsewhere in documenting the environmental impacts of different diets, very little work on this has been undertaken in the US, which might help explain their decision. To address this gap, we developed a novel approach to study the environmental impacts of individual food choices in the US. Individual 24‐hour recall data (N=28,276) from the National Health and Nutrition Examination Survey for 2005–2010 were converted to commodity form using resources from the US Environmental Protection Agency. There were 2.63 million food item/recipe components consumed by these individuals on the two days of recall, and these were converted to 461 different commodities. The environmental impacts of these food commodities – principally greenhouse gas emissions – were obtained from a comprehensive review of published life cycle assessment (LCA) studies. The LCA approach assesses inputs and outputs in the production, distribution, and consumption of products, and has seen increased application to foods in recent years. By matching the food choices of individuals to environmental impacts, we can quantify the impact of dietary choices on greenhouse gas emissions and other environmental impacts. Using aggregate agricultural food balance sheet data, we previously estimated mean greenhouse gas emissions from the U.S. diet to be 5.0 kg of carbon dioxide equivalents per person per day. The approach reported here will allow us to refine that estimate, and analyze the variation in the US population of this outcome by demographic and socio‐economic characteristics, as well as by diet knowledge and health behaviors. This cross‐disciplinary research demonstrates an approach that can inform future policy discussions regarding dietary recommendations and their potential impacts on sustainability.Support or Funding InformationThis work was supported by the Wellcome Trust (grant # 106854/Z/15/Z).

A systematic analysis of the data pertaining to the disposal method of the drugs collected by National Prescription Drug Take‐Back Day has been performed in association with United States Drug Enforcement Administration's (US‐DEA's) – Department of Justice (DOJ), DEA Public Affairs, Washington D.C. Based on the data collected from the National Prescription Drug Take‐Back Day all across United States by US DEA–DOJ, as of September 5, 2014, an estimated 4.1 million pounds (2,123 tons) of prescription medications have been removed from the circulation. As per the US DEA b– DOJ public affairs, the drugs that are collected by this program were disposed by incineration facility monitored and regulated by the United States – Environmental Protection Agency (US‐EPA). The entire disposal of the drugs that are collected by National Prescription Drug Take ‐ Back day is completed by a vendor destined by US DEA ‐DOJ. Further analysis of the disposal process reveal following pitfalls of this process: i. There are no data on file regarding pollutants generated from the incineration of Drugs from the take back programs by US DEA ‐ DOJ, 2. The practice of incineration at the rate of en mass is a potential resource for reaction intermediates, such as dioxins, fly ash, and other unknown pollutants, 3. The practice of not sorting the drugs according to the chemical toxicity prior to incineration potential harm to the environment and biota. Specific information on the class of the medication as per the chemical potencies for generating combustion based pollutants are investigated. Data analysis on the Impact of the disposal practices of drugs from take back day will be presented in Experimental Biology 2016.Support or Funding InformationProfessional Development Funds to S.Kannan at SWTJC for 2014–2015

Background: Silver nanoparticles (AgNPs) have been widely applied in research and industrial fields, finding applications in nanomedicine, drug delivery, biomedical devices, electronics, the energy sector, and environmental protection. Patents provide information on the industrial viability of product technologies, and the number of patent documents provides an estimate of the evolution of a specific technological field. Aims: The present work aims to describe the current trends in AgNPs patent applications. In addition, a retrospective study of published patents in Brazil is presented. Methods: Analyses of AgNPs-related patents were conducted using the free platform for patent search Lens® in 2010-2019 and articles published in same period using the Scholar® base. The patent applications and their evolution over time, major depositors and holders, and the main technological areas associated with AgNP applications have been described. Results: China and United States are the major patent applicants for nanotechnologies. The worldwide distribution of publications of journal articles shows that China, India, and the United States are the leading countries in the total number of articles published, in that order. Conclusion: Our study of patent applications and published articles confirmed the growing global increase in new technologies involving NPs and AgNPs, particularly in the biotechnology area, in the fields of medicine and agriculture.

Although the US is the second highest‐ranked country in the world in greenhouse gas emissions (GHGE), and food production is a significant contributor to this, little is known about the impact of individual food choices in the US on GHGE or how this might relate to nutrient intakes. To address this gap, we developed a novel approach to study the environmental impacts of individual food choices in the US. Individual 24‐hour recall data on foods consumed by adults, 18–65 years of age (N= 13,204), from the National Health and Nutrition Examination Survey (NHANES) for 2005–2010 were converted to commodity form using resources from the US Environmental Protection Agency. The GHGE of these commodities were aggregated from a comprehensive review of life cycle assessment studies, which estimate environmental impacts throughout the “life” of a product, in this case foods. After matching the food choices of individuals to these GHGE, we ranked their 1‐day diets into quintiles based on GHGE per 1000 kilocalories, and compared the lowest and highest GHGE quintile groups. We focused on 12 key nutrients of concern that were identified in the Dietary Guidelines for Americans as either being under‐consumed by the US population or over‐consumed by it. T‐tests for differences in means were conducted using Stata 13.0 and made use of sample weights and survey design parameters published with the datasets. We estimate that the production of foods consumed by U.S. adults contributed 5.49 carbon dioxide‐equivalents per person per day (95% CI = 5.38 to 5.60), a value which is within the range of GHGE impacts found in European countries. The lowest GHGE diets (bottom quintile) scored better on five of the key nutrients, with significantly (p < 0.001) more vitamin E, folate, and dietary fiber per 1000 kilocalories and significantly (p < 0.001) less sodium and saturated fat than the highest GHGE diets. However, there was a higher content of three of the nutrients ‐‐ calcium, vitamin D, and potassium ‐‐ in the highest GHGE diets. We found similar results when limiting the sample to only those recalls that respondents identified as representing a “usual” amount. These results suggest that food patterns which are less environmentally impactful are more nutritious on several key dimensions, although not on all of them. The links between food choice, nutritional outcomes and environmental impacts are nuanced, which calls for more research and understanding of these interactions.Support or Funding InformationThis work was supported by the Wellcome Trust (grant # 106854/Z/15/Z).

AbstractPublic trust in government agencies plays an important role in the formation of public opinion about public policy issues. However, the association between public trust in regulatory agencies and public support for policy development in emergent biotechnologies such as gene drive is not well understood. The United States Department of Agriculture (USDA), the Food and Drug Administration (FDA), and the Environmental Protection Agency (EPA) are tasked with coordinating and regulating biotechnology. Drawing on past literature, this study examines how public trust in these federal agencies is associated with public opinion on various options for gene drive policy. Using data from a nationally representative public opinion survey (n = 1220) conducted in 2021, our statistical analyses show that respondents who report higher levels of trust in regulatory agencies are more likely to support policy proposals that promote gene drive research and ultimately, may lead to regulatory policies that allow gene drive to be researched and employed to manage agricultural pests, establishing a pathway for scientists, developers, producers, and consumers alike to realize the benefits of this technology.

An effort has been to demonstrate that the incineration of Prescription Drug en masse impart potential environmental hazard. According to http://www.natracare.com/en‐GB/ the current data shows that even in “state‐of‐the‐art” incinerators, burning hazardous waste will lead to the release of three types of dangerous pollutants into our environment: heavy metals; unburned toxic chemicals; and new pollutants ‐ entirely new chemicals formed during the incineration process (Verbatim). According to the US Environmental Protection Authority: “Fugitive emissions and accidental spills may release as much or even more toxic material into the environment than direct emissions from incomplete waste incineration.” According to Greenpeace, studies have identified up to 43 different semi‐volatile, organic chemicals in incinerator ash, and at least 16 organic chemicals in scrubber water from hazardous waste incinerators. Ash is commonly buried in landfill, while effluent is often treated before being discharged into rivers or lakes. Fragments of partially burned waste chemicals recombine within incinerator furnaces, smokestacks, and/or pollution control devices. One study identified 250 volatile organic compounds, many of which are known to be highly toxic or carcinogenic. Among the possible compounds are dioxins and furans, often referred to as just dioxins suppression of the immune system, diabetes, organ toxicity and a wide range of effects on hormones. It is estimated that for every three tonnes of waste that is incinerated, one tonne of ash is generated. Projection analysis on the amount of fly ash generated due to the incineration of drugs from National Drug Take Back day (NDTBD) by United States Drug Enforcement Administration – Department of Justice (US‐DEA‐DOJ) mount 3 fold increase in the environmental contamination. However, taking into account of anaerobic digestion of the drugs from NDTBD – US‐DEA‐DOJ could potentially decrease the methane emissions by 5 – 7 folds compare to the industrial chemicals disposal standard. Taken together, the projection analysis data indicate that there is a statistically significant increase in the environmental contamination by incineration the drugs from NDTBD – US‐DEA‐DOJ. Data analysis for the environmental impact assessment of chemical pollutant will be presented at EB 2016.Support or Funding InformationProfessional Development Funds provided to S. Kannan at SWTJC for 2014–2015

Abstract Background Gastrointestinal nematode infection (GNI) is the most important disease affecting the small ruminant industry in U.S. The environmental conditions in the southern United States are ideal for the survival of the most pathogenic gastrointestinal nematode, Haemonchus contortus. Host genetic variation for resistance to H. contortus allows selective breeding for increased resistance of animals. This selection process increases the prevalence of particular alleles in sheep and goats and creates unique genetic patterns in the genome of these species. The aim of this study was to identify loci with divergent allelic frequencies in a candidate gene panel of 100 genes using two different approaches (frequentist and Bayesian) to estimate Fst outliers in three different breeds of sheep and goats exposed to H. contortus. Results Our results for sheep populations showed SNPs under selection in C3AR1, CSF3, SOCS2, NOS2, STAT5B, TGFB2 and IL2RA genes using frequentist and Bayesian approaches. For goats, SNPs in CD1D, ITGA9, IL12A, IL13RA1, CD86 and TGFB2 genes were under selection. Common signatures of selection in both species were observed in NOS2, TGFB2 and TLR4 genes. Directional selection was present in all SNPs evaluated in the present study. Conclusions A total of 13 SNPs within 7 genes of our candidate gene panel related to H. contortus exposure were identified under selection in sheep populations. For goats, 11 SNPs within 7 genes were identified under selection. Results from this study support the hypothesis that resistance to H. contortus is likely to be controlled by many loci. Shared signatures of selection related to mechanisms of immune protection against H. contortus infection in sheep and goats could be useful targets in breeding programs aimed to produce resistant animals with low FEC.

The articlecompares and contrasts the business environment of Georgia and the world's largest economy, the United States of America. PESTEL analysis was used for the political, economic, social, technological, environmental and legal factors that have a significant impact on both country's macro environments. The PESTEL analysis outlines the current trends, priorities, goals and objectives of the two countries. Cooperation between Georgia and the United States of America in the political, economic and cultural spheres has a long history. The United States of America and Georgia each considers the other a strategic ally. The bilateral relations of the countries have undergone qualitative changes. Friendship based on equality and respect for state sovereignty distinguishes the strategic relationship between these two countries. Leading international organizations 2017-2021 reports were used to analyze the factors of the countries economic, investment and financial indicators. According to the obtained results, relevant conclusions were made; The rating scores of Georgia and the United States of Americawere also studied. According to the 2020 report presented by the international analytical and research organization The Economist Intelligence Unit, the USA remains in the category of "deficient democracy", which was removed from the category of "full democracy" in 2016 due to the erosion of public trust in the country's institutions. Georgia, as a "hybrid regime" country, has a low score in the world rating. Democratic institutions and the rule of law are not enough to sustain a successful democracy. It is important to strengthen the civil society sector and involve them in policy discussions. People's involvement in democratic and accountable decision-making is a prerequisite for a truly active democracy. The USA has trade relations with more than 200 countries. The United States is the second largest exporter of goods in the world, Georgia ranks 121st in terms of exports. According to the Legatum Institute's 2019-2020 Prosperity Index, which measures well-being in 167 countries around the world, Georgia is ranked 53rd, behind the US, which ranks a rather high 18th in the world.In the Doing Business 2020 report presented by the World Bank, Georgia is among the leaders in the ease of doing business. Among 190 economies of the world, Georgia is in 7th place with a score of 83.7, and the United States is in 6th place with a score of 84.0. The business environment of Georgia faced significant challenges in the last period, 2019-2020. The Global Competitiveness Report published by the Economic Forum comprehensively measures a country's competitiveness, the quality of the macroeconomic environment, the state of institutions and technological achievements. According to the Global Competitiveness Index, during the analysis period of 2019, among 141 countries Georgia improved its position the 74th place, with a total of 60.6 points, and the USA took the 2nd place with 83.7 points. Georgia's competitiveness depends on many factors, including macroeconomicstability, improvement of infrastructure, healthcare, education and standard of living. Improvement of production level, implementation of new technologies and a number of other important factors in long-term planning and implementation also played a factor. By increasing international competitiveness, Georgia can drastically reduce unemployment and poverty levels and achieve stable economic growth.The Heritage Foundation's Index of Economic Freedom annually examines 180 countries and determines their level of freedom. According to the 2020 study, Georgia advanced to the 12th position in the world ranking and earned a historical high of 77.1 points. For the growth of the country's economy it is necessary to attract investments which requires the creation of a favorable investment climate in the country. One of the most urgent requirements of the economic policy of Georgiais to promote the integrated and consistent development of competitiveness and growth factors. The Gini coefficient in economics, as calculated by the World Bank, is a measure of statistical dispersion that measures income inequality andwealth inequality within a nation. From the 2018-2019 report, it is clear how much Georgia's income inequality indicators lag behind the USA. Georgia has made significant progress in creating innovative digital services for business development.It has, however, only made a small amount of progress in terms of firm’s technological development and innovative capabilities. Despite the overall weak performance, the United States of America remains one of the most competitive economies in the world. It is still a center of innovation, leading in technology improvement and development in areas such as nanotechnology, environmental technology and biotechnology. Air pollution is a growing environmental challenge for Georgia and the USA. Indoor and outdoor air pollution has a significant impact on human health. Protection of the environment, maintaining its sustainability and rational use of natural resources, along with the sustainable development of agriculture, represents an important challenge and is one of the priority directions of the Government of Georgia. In the Corruption Perception Index of Transparency International, which measures the level of corruption perception in the public sector and is based on the assessments of businesses and experts, compared to the 2020-2019 data Georgia is represented in the 45th place with a total of 55 points decrease. As for the USA, with a decrease of 67 points, it is in the 27thplace. The article illustrates that despite the implementation of a number of systemic reforms in Georgia, the country’s indicators in the world rankings are relatively low.This requires additional efforts from the governmentwhich should be aimed at improving the business environment. Keywords: Georgia, USA, Business Environment, PESTEL Analysis, Factors. JEL Codes: M20, M21, M29

The Environmental Protection Agency (EPA) reports a significant number of heavy metal-contaminated sites across the United States. To address this public health concern, rhizoremediation using microbes has emerged as a promising solution, considering the limitations and inefficiencies of current approaches. We hypothesized that if Pseudomonas fluorescens, Burkholderia vietnamiensis, and Rhizobium leguminosarum are cultivated in the rhizospheres (area around the plant roots) of Brassica juncea, Oryza sativa, or Pisum sativum in lead-contaminated soil, then a significant reduction in soil-lead content should be observed. To determine the most effective soil microbe, we obtained raw sequences of 16s rRNA from 96 soil samples from the National Center for Biotechnology Information and processed the sequences through Qiime2 to examine bacterial taxonomy in lead-contaminated and uncontaminated rhizospheres. A combination of soil microbes – P. fluorescens, B. vietnamiensis, and R. leguminosarum – were inoculated in the rhizosphere of B. juncea, O. sativa, and P. sativum in soil contaminated with 500 parts per million (ppm) of lead. Soil lead content was measured at various stages of plant growth. After four weeks, we noticed a 70% decline in the lead content with P. fluorescens-B. juncea combination and a 90% decline with P. fluorescens-R. leguminosarum-B. vietnamiensis triple combination with B. juncea. Chlorophyll content analysis of the dried leaves of plant groups showed similar optical density to control leaves, indicating that lead decontamination in the soil did not negatively affect plant health. Therefore, rhizoremediation is an effective bioremediation strategy and may increase crop productivity by converting nonarable lands into arable lands.

Photo ID 158378414 © Eduard Muzhevskyi | Dreamstime.com ABSTRACT There is a debate about the ethical implications of using human embryos in stem cell research, which can be influenced by cultural, moral, and social values. This paper argues for an adaptable framework to accommodate diverse cultural and religious perspectives. By using an adaptive ethics model, research protections can reflect various populations and foster growth in stem cell research possibilities. INTRODUCTION Stem cell research combines biology, medicine, and technology, promising to alter health care and the understanding of human development. Yet, ethical contention exists because of individuals’ perceptions of using human embryos based on their various cultural, moral, and social values. While these disagreements concerning policy, use, and general acceptance have prompted the development of an international ethics policy, such a uniform approach can overlook the nuanced ethical landscapes between cultures. With diverse viewpoints in public health, a single global policy, especially one reflecting Western ethics or the ethics prevalent in high-income countries, is impractical. This paper argues for a culturally sensitive, adaptable framework for the use of embryonic stem cells. Stem cell policy should accommodate varying ethical viewpoints and promote an effective global dialogue. With an extension of an ethics model that can adapt to various cultures, we recommend localized guidelines that reflect the moral views of the people those guidelines serve. BACKGROUND Stem cells, characterized by their unique ability to differentiate into various cell types, enable the repair or replacement of damaged tissues. Two primary types of stem cells are somatic stem cells (adult stem cells) and embryonic stem cells. Adult stem cells exist in developed tissues and maintain the body’s repair processes.[1] Embryonic stem cells (ESC) are remarkably pluripotent or versatile, making them valuable in research.[2] However, the use of ESCs has sparked ethics debates. Considering the potential of embryonic stem cells, research guidelines are essential. The International Society for Stem Cell Research (ISSCR) provides international stem cell research guidelines. They call for “public conversations touching on the scientific significance as well as the societal and ethical issues raised by ESC research.”[3] The ISSCR also publishes updates about culturing human embryos 14 days post fertilization, suggesting local policies and regulations should continue to evolve as ESC research develops.[4] Like the ISSCR, which calls for local law and policy to adapt to developing stem cell research given cultural acceptance, this paper highlights the importance of local social factors such as religion and culture. I. Global Cultural Perspective of Embryonic Stem Cells Views on ESCs vary throughout the world. Some countries readily embrace stem cell research and therapies, while others have stricter regulations due to ethical concerns surrounding embryonic stem cells and when an embryo becomes entitled to moral consideration. The philosophical issue of when the “someone” begins to be a human after fertilization, in the morally relevant sense,[5] impacts when an embryo becomes not just worthy of protection but morally entitled to it. The process of creating embryonic stem cell lines involves the destruction of the embryos for research.[6] Consequently, global engagement in ESC research depends on social-cultural acceptability. a. US and Rights-Based Cultures In the United States, attitudes toward stem cell therapies are diverse. The ethics and social approaches, which value individualism,[7] trigger debates regarding the destruction of human embryos, creating a complex regulatory environment. For example, the 1996 Dickey-Wicker Amendment prohibited federal funding for the creation of embryos for research and the destruction of embryos for “more than allowed for research on fetuses in utero.”[8] Following suit, in 2001, the Bush Administration heavily restricted stem cell lines for research. However, the Stem Cell Research Enhancement Act of 2005 was proposed to help develop ESC research but was ultimately vetoed.[9] Under the Obama administration, in 2009, an executive order lifted restrictions allowing for more development in this field.[10] The flux of research capacity and funding parallels the different cultural perceptions of human dignity of the embryo and how it is socially presented within the country’s research culture.[11] b. Ubuntu and Collective Cultures African bioethics differs from Western individualism because of the different traditions and values. African traditions, as described by individuals from South Africa and supported by some studies in other African countries, including Ghana and Kenya, follow the African moral philosophies of Ubuntu or Botho and Ukama, which “advocates for a form of wholeness that comes through one’s relationship and connectedness with other people in the society,”[12] making autonomy a socially collective concept. In this context, for the community to act autonomously, individuals would come together to decide what is best for the collective. Thus, stem cell research would require examining the value of the research to society as a whole and the use of the embryos as a collective societal resource. If society views the source as part of the collective whole, and opposes using stem cells, compromising the cultural values to pursue research may cause social detachment and stunt research growth.[13] Based on local culture and moral philosophy, the permissibility of stem cell research depends on how embryo, stem cell, and cell line therapies relate to the community as a whole. Ubuntu is the expression of humanness, with the person’s identity drawn from the “’I am because we are’” value.[14] The decision in a collectivistic culture becomes one born of cultural context, and individual decisions give deference to others in the society. Consent differs in cultures where thought and moral philosophy are based on a collective paradigm. So, applying Western bioethical concepts is unrealistic. For one, Africa is a diverse continent with many countries with different belief systems, access to health care, and reliance on traditional or Western medicines. Where traditional medicine is the primary treatment, the “’restrictive focus on biomedically-related bioethics’” [is] problematic in African contexts because it neglects bioethical issues raised by traditional systems.”[15] No single approach applies in all areas or contexts. Rather than evaluating the permissibility of ESC research according to Western concepts such as the four principles approach, different ethics approaches should prevail. Another consideration is the socio-economic standing of countries. In parts of South Africa, researchers have not focused heavily on contributing to the stem cell discourse, either because it is not considered health care or a health science priority or because resources are unavailable.[16] Each country’s priorities differ given different social, political, and economic factors. In South Africa, for instance, areas such as maternal mortality, non-communicable diseases, telemedicine, and the strength of health systems need improvement and require more focus[17] Stem cell research could benefit the population, but it also could divert resources from basic medical care. Researchers in South Africa adhere to the National Health Act and Medicines Control Act in South Africa and international guidelines; however, the Act is not strictly enforced, and there is no clear legislation for research conduct or ethical guidelines.[18] Some parts of Africa condemn stem cell research. For example, 98.2 percent of the Tunisian population is Muslim.[19] Tunisia does not permit stem cell research because of moral conflict with a Fatwa. Religion heavily saturates the regulation and direction of research.[20] Stem cell use became permissible for reproductive purposes only recently, with tight restrictions preventing cells from being used in any research other than procedures concerning ART/IVF. Their use is conditioned on consent, and available only to married couples.[21] The community's receptiveness to stem cell research depends on including communitarian African ethics. c. Asia Some Asian countries also have a collective model of ethics and decision making.[22] In China, the ethics model promotes a sincere respect for life or human dignity,[23] based on protective medicine. This model, influenced by Traditional Chinese Medicine (TCM), [24] recognizes Qi as the vital energy delivered via the meridians of the body; it connects illness to body systems, the body’s entire constitution, and the universe for a holistic bond of nature, health, and quality of life.[25] Following a protective ethics model, and traditional customs of wholeness, investment in stem cell research is heavily desired for its applications in regenerative therapies, disease modeling, and protective medicines. In a survey of medical students and healthcare practitioners, 30.8 percent considered stem cell research morally unacceptable while 63.5 percent accepted medical research using human embryonic stem cells. Of these individuals, 89.9 percent supported increased funding for stem cell research.[26] The scientific community might not reflect the overall population. From 1997 to 2019, China spent a total of $576 million (USD) on stem cell research at 8,050 stem cell programs, increased published presence from 0.6 percent to 14.01 percent of total global stem cell publications as of 2014, and made significant strides in cell-based therapies for various medical conditions.[27] However, while China has made substantial investments in stem cell research and achieved notable progress in clinical applications, concerns linger regarding ethical oversight and transparency.[28] For example, the China Biosecurity Law, promoted by the National Health Commission and China Hospital Association, attempted to mitigate risks by introducing an institutional review board (IRB) in the regulatory bodies. 5800 IRBs registered with the Chinese Clinical Trial Registry since 2021.[29] However, issues still need to be addressed in implementing effective IRB review and approval procedures. The substantial government funding and focus on scientific advancement have sometimes overshadowed considerations of regional cultures, ethnic minorities, and individual perspectives, particularly evident during the one-child policy era. As government policy adapts to promote public stability, such as the change from the one-child to the two-child policy,[30] research ethics should also adapt to ensure respect for the values of its represented peoples. Japan is also relatively supportive of stem cell research and therapies. Japan has a more transparent regulatory framework, allowing for faster approval of regenerative medicine products, which has led to several advanced clinical trials and therapies.[31] South Korea is also actively engaged in stem cell research and has a history of breakthroughs in cloning and embryonic stem cells.[32] However, the field is controversial, and there are issues of scientific integrity. For example, the Korean FDA fast-tracked products for approval,[33] and in another instance, the oocyte source was unclear and possibly violated ethical standards.[34] Trust is important in research, as it builds collaborative foundations between colleagues, trial participant comfort, open-mindedness for complicated and sensitive discussions, and supports regulatory procedures for stakeholders. There is a need to respect the culture’s interest, engagement, and for research and clinical trials to be transparent and have ethical oversight to promote global research discourse and trust. d. Middle East Countries in the Middle East have varying degrees of acceptance of or restrictions to policies related to using embryonic stem cells due to cultural and religious influences. Saudi Arabia has made significant contributions to stem cell research, and conducts research based on international guidelines for ethical conduct and under strict adherence to guidelines in accordance with Islamic principles. Specifically, the Saudi government and people require ESC research to adhere to Sharia law. In addition to umbilical and placental stem cells,[35] Saudi Arabia permits the use of embryonic stem cells as long as they come from miscarriages, therapeutic abortions permissible by Sharia law, or are left over from in vitro fertilization and donated to research.[36] Laws and ethical guidelines for stem cell research allow the development of research institutions such as the King Abdullah International Medical Research Center, which has a cord blood bank and a stem cell registry with nearly 10,000 donors.[37] Such volume and acceptance are due to the ethical ‘permissibility’ of the donor sources, which do not conflict with religious pillars. However, some researchers err on the side of caution, choosing not to use embryos or fetal tissue as they feel it is unethical to do so.[38] Jordan has a positive research ethics culture.[39] However, there is a significant issue of lack of trust in researchers, with 45.23 percent (38.66 percent agreeing and 6.57 percent strongly agreeing) of Jordanians holding a low level of trust in researchers, compared to 81.34 percent of Jordanians agreeing that they feel safe to participate in a research trial.[40] Safety testifies to the feeling of confidence that adequate measures are in place to protect participants from harm, whereas trust in researchers could represent the confidence in researchers to act in the participants’ best interests, adhere to ethical guidelines, provide accurate information, and respect participants’ rights and dignity. One method to improve trust would be to address communication issues relevant to ESC. Legislation surrounding stem cell research has adopted specific language, especially concerning clarification “between ‘stem cells’ and ‘embryonic stem cells’” in translation.[41] Furthermore, legislation “mandates the creation of a national committee… laying out specific regulations for stem-cell banking in accordance with international standards.”[42] This broad regulation opens the door for future global engagement and maintains transparency. However, these regulations may also constrain the influence of research direction, pace, and accessibility of research outcomes. e. Europe In the European Union (EU), ethics is also principle-based, but the principles of autonomy, dignity, integrity, and vulnerability are interconnected.[43] As such, the opportunity for cohesion and concessions between individuals’ thoughts and ideals allows for a more adaptable ethics model due to the flexible principles that relate to the human experience The EU has put forth a framework in its Convention for the Protection of Human Rights and Dignity of the Human Being allowing member states to take different approaches. Each European state applies these principles to its specific conventions, leading to or reflecting different acceptance levels of stem cell research. [44] For example, in Germany, Lebenzusammenhang, or the coherence of life, references integrity in the unity of human culture. Namely, the personal sphere “should not be subject to external intervention.”[45] Stem cell interventions could affect this concept of bodily completeness, leading to heavy restrictions. Under the Grundgesetz, human dignity and the right to life with physical integrity are paramount.[46] The Embryo Protection Act of 1991 made producing cell lines illegal. Cell lines can be imported if approved by the Central Ethics Commission for Stem Cell Research only if they were derived before May 2007.[47] Stem cell research respects the integrity of life for the embryo with heavy specifications and intense oversight. This is vastly different in Finland, where the regulatory bodies find research more permissible in IVF excess, but only up to 14 days after fertilization.[48] Spain’s approach differs still, with a comprehensive regulatory framework.[49] Thus, research regulation can be culture-specific due to variations in applied principles. Diverse cultures call for various approaches to ethical permissibility.[50] Only an adaptive-deliberative model can address the cultural constructions of self and achieve positive, culturally sensitive stem cell research practices.[51] II. Religious Perspectives on ESC Embryonic stem cell sources are the main consideration within religious contexts. While individuals may not regard their own religious texts as authoritative or factual, religion can shape their foundations or perspectives. The Qur'an states: “And indeed We created man from a quintessence of clay. Then We placed within him a small quantity of nutfa (sperm to fertilize) in a safe place. Then We have fashioned the nutfa into an ‘alaqa (clinging clot or cell cluster), then We developed the ‘alaqa into mudgha (a lump of flesh), and We made mudgha into bones, and clothed the bones with flesh, then We brought it into being as a new creation. So Blessed is Allah, the Best of Creators.”[52] Many scholars of Islam estimate the time of soul installment, marked by the angel breathing in the soul to bring the individual into creation, as 120 days from conception.[53] Personhood begins at this point, and the value of life would prohibit research or experimentation that could harm the individual. If the fetus is more than 120 days old, the time ensoulment is interpreted to occur according to Islamic law, abortion is no longer permissible.[54] There are a few opposing opinions about early embryos in Islamic traditions. According to some Islamic theologians, there is no ensoulment of the early embryo, which is the source of stem cells for ESC research.[55] In Buddhism, the stance on stem cell research is not settled. The main tenets, the prohibition against harming or destroying others (ahimsa) and the pursuit of knowledge (prajña) and compassion (karuna), leave Buddhist scholars and communities divided.[56] Some scholars argue stem cell research is in accordance with the Buddhist tenet of seeking knowledge and ending human suffering. Others feel it violates the principle of not harming others. Finding the balance between these two points relies on the karmic burden of Buddhist morality. In trying to prevent ahimsa towards the embryo, Buddhist scholars suggest that to comply with Buddhist tenets, research cannot be done as the embryo has personhood at the moment of conception and would reincarnate immediately, harming the individual's ability to build their karmic burden.[57] On the other hand, the Bodhisattvas, those considered to be on the path to enlightenment or Nirvana, have given organs and flesh to others to help alleviate grieving and to benefit all.[58] Acceptance varies on applied beliefs and interpretations. Catholicism does not support embryonic stem cell research, as it entails creation or destruction of human embryos. This destruction conflicts with the belief in the sanctity of life. For example, in the Old Testament, Genesis describes humanity as being created in God’s image and multiplying on the Earth, referencing the sacred rights to human conception and the purpose of development and life. In the Ten Commandments, the tenet that one should not kill has numerous interpretations where killing could mean murder or shedding of the sanctity of life, demonstrating the high value of human personhood. In other books, the theological conception of when life begins is interpreted as in utero,[59] highlighting the inviolability of life and its formation in vivo to make a religious point for accepting such research as relatively limited, if at all.[60] The Vatican has released ethical directives to help apply a theological basis to modern-day conflicts. The Magisterium of the Church states that “unless there is a moral certainty of not causing harm,” experimentation on fetuses, fertilized cells, stem cells, or embryos constitutes a crime.[61] Such procedures would not respect the human person who exists at these stages, according to Catholicism. Damages to the embryo are considered gravely immoral and illicit.[62] Although the Catholic Church officially opposes abortion, surveys demonstrate that many Catholic people hold pro-choice views, whether due to the context of conception, stage of pregnancy, threat to the mother’s life, or for other reasons, demonstrating that practicing members can also accept some but not all tenets.[63] Some major Jewish denominations, such as the Reform, Conservative, and Reconstructionist movements, are open to supporting ESC use or research as long as it is for saving a life.[64] Within Judaism, the Talmud, or study, gives personhood to the child at birth and emphasizes that life does not begin at conception:[65] “If she is found pregnant, until the fortieth day it is mere fluid,”[66] Whereas most religions prioritize the status of human embryos, the Halakah (Jewish religious law) states that to save one life, most other religious laws can be ignored because it is in pursuit of preservation.[67] Stem cell research is accepted due to application of these religious laws. We recognize that all religions contain subsets and sects. The variety of environmental and cultural differences within religious groups requires further analysis to respect the flexibility of religious thoughts and practices. We make no presumptions that all cultures require notions of autonomy or morality as under the common morality theory, which asserts a set of universal moral norms that all individuals share provides moral reasoning and guides ethical decisions.[68] We only wish to show that the interaction with morality varies between cultures and countries. III. A Flexible Ethical Approach The plurality of different moral approaches described above demonstrates that there can be no universally acceptable uniform law for ESC on a global scale. Instead of developing one standard, flexible ethical applications must be continued. We recommend local guidelines that incorporate important cultural and ethical priorities. While the Declaration of Helsinki is more relevant to people in clinical trials receiving ESC products, in keeping with the tradition of protections for research subjects, consent of the donor is an ethical requirement for ESC donation in many jurisdictions including the US, Canada, and Europe.[69] The Declaration of Helsinki provides a reference point for regulatory standards and could potentially be used as a universal baseline for obtaining consent prior to gamete or embryo donation. For instance, in Columbia University’s egg donor program for stem cell research, donors followed standard screening protocols and “underwent counseling sessions that included information as to the purpose of oocyte donation for research, what the oocytes would be used for, the risks and benefits of donation, and process of oocyte stimulation” to ensure transparency for consent.[70] The program helped advance stem cell research and provided clear and safe research methods with paid participants. Though paid participation or covering costs of incidental expenses may not be socially acceptable in every culture or context,[71] and creating embryos for ESC research is illegal in many jurisdictions, Columbia’s program was effective because of the clear and honest communications with donors, IRBs, and related stakeholders. This example demonstrates that cultural acceptance of scientific research and of the idea that an egg or embryo does not have personhood is likely behind societal acceptance of donating eggs for ESC research. As noted, many countries do not permit the creation of embryos for research. Proper communication and education regarding the process and purpose of stem cell research may bolster comprehension and garner more acceptance. “Given the sensitive subject material, a complete consent process can support voluntary participation through trust, understanding, and ethical norms from the cultures and morals participants value. This can be hard for researchers entering countries of different socioeconomic stability, with different languages and different societal values.[72] An adequate moral foundation in medical ethics is derived from the cultural and religious basis that informs knowledge and actions.[73] Understanding local cultural and religious values and their impact on research could help researchers develop humility and promote inclusion. IV. Concerns Some may argue that if researchers all adhere to one ethics standard, protection will be satisfied across all borders, and the global public will trust researchers. However, defining what needs to be protected and how to define such research standards is very specific to the people to which standards are applied. We suggest that applying one uniform guide cannot accurately protect each individual because we all possess our own perceptions and interpretations of social values.[74] Therefore, the issue of not adjusting to the moral pluralism between peoples in applying one standard of ethics can be resolved by building out ethics models that can be adapted to different cultures and religions. Other concerns include medical tourism, which may promote health inequities.[75] Some countries may develop and approve products derived from ESC research before others, compromising research ethics or drug approval processes. There are also concerns about the sale of unauthorized stem cell treatments, for example, those without FDA approval in the United States. Countries with robust research infrastructures may be tempted to attract medical tourists, and some customers will have false hopes based on aggressive publicity of unproven treatments.[76] For example, in China, stem cell clinics can market to foreign clients who are not protected under the regulatory regimes. Companies employ a marketing strategy of “ethically friendly” therapies. Specifically, in the case of Beike, China’s leading stem cell tourism company and sprouting network, ethical oversight of administrators or health bureaus at one site has “the unintended consequence of shifting questionable activities to another node in Beike's diffuse network.”[77] In contrast, Jordan is aware of stem cell research’s potential abuse and its own status as a “health-care hub.” Jordan’s expanded regulations include preserving the interests of individuals in clinical trials and banning private companies from ESC research to preserve transparency and the integrity of research practices.[78] The social priorities of the community are also a concern. The ISSCR explicitly states that guidelines “should be periodically revised to accommodate scientific advances, new challenges, and evolving social priorities.”[79] The adaptable ethics model extends this consideration further by addressing whether research is warranted given the varying degrees of socioeconomic conditions, political stability, and healthcare accessibilities and limitations. An ethical approach would require discussion about resource allocation and appropriate distribution of funds.[80] CONCLUSION While some religions emphasize the sanctity of life from conception, which may lead to public opposition to ESC research, others encourage ESC research due to its potential for healing and alleviating human pain. Many countries have special regulations that balance local views on embryonic personhood, the benefits of research as individual or societal goods, and the protection of human research subjects. To foster understanding and constructive dialogue, global policy frameworks should prioritize the protection of universal human rights, transparency, and informed consent. In addition to these foundational global policies, we recommend tailoring local guidelines to reflect the diverse cultural and religious perspectives of the populations they govern. Ethics models should be adapted to local populations to effectively establish research protections, growth, and possibilities of stem cell research. For example, in countries with strong beliefs in the moral sanctity of embryos or heavy religious restrictions, an adaptive model can allow for discussion instead of immediate rejection. In countries with limited individual rights and voice in science policy, an adaptive model ensures cultural, moral, and religious views are taken into consideration, thereby building social inclusion. While this ethical consideration by the government may not give a complete voice to every individual, it will help balance policies and maintain the diverse perspectives of those it affects. Embracing an adaptive ethics model of ESC research promotes open-minded dialogue and respect for the importance of human belief and tradition. By actively engaging with cultural and religious values, researchers can better handle disagreements and promote ethical research practices that benefit each society. This brief exploration of the religious and cultural differences that impact ESC research reveals the nuances of relative ethics and highlights a need for local policymakers to apply a more intense adaptive model. - [1] Poliwoda, S., Noor, N., Downs, E., Schaaf, A., Cantwell, A., Ganti, L., Kaye, A. D., Mosel, L. I., Carroll, C. B., Viswanath, O., & Urits, I. (2022). Stem cells: a comprehensive review of origins and emerging clinical roles in medical practice. Orthopedic reviews, 14(3), 37498. https://doi.org/10.52965/001c.37498 [2] Poliwoda, S., Noor, N., Downs, E., Schaaf, A., Cantwell, A., Ganti, L., Kaye, A. D., Mosel, L. I., Carroll, C. B., Viswanath, O., & Urits, I. (2022). Stem cells: a comprehensive review of origins and emerging clinical roles in medical practice. Orthopedic reviews, 14(3), 37498. https://doi.org/10.52965/001c.37498 [3] International Society for Stem Cell Research. (2023). Laboratory-based human embryonic stem cell research, embryo research, and related research activities. International Society for Stem Cell Research. https://www.isscr.org/guidelines/blog-post-title-one-ed2td-6fcdk; Kimmelman, J., Hyun, I., Benvenisty, N. et al. Policy: Global standards for stem-cell research. Nature 533, 311–313 (2016). https://doi.org/10.1038/533311a [4] International Society for Stem Cell Research. (2023). Laboratory-based human embryonic stem cell research, embryo research, and related research activities. International Society for Stem Cell Research. https://www.isscr.org/guidelines/blog-post-title-one-ed2td-6fcdk [5] Concerning the moral philosophies of stem cell research, our paper does not posit a personal moral stance nor delve into the “when” of human life begins. To read further about the philosophical debate, consider the following sources: Sandel M. J. (2004). Embryo ethics--the moral logic of stem-cell research. The New England journal of medicine, 351(3), 207–209. https://doi.org/10.1056/NEJMp048145; George, R. P., & Lee, P. (2020, September 26). Acorns and Embryos. The New Atlantis. https://www.thenewatlantis.com/publications/acorns-and-embryos; Sagan, A., & Singer, P. (2007). The moral status of stem cells. Metaphilosophy, 38(2/3), 264–284. http://www.jstor.org/stable/24439776; McHugh P. R. (2004). Zygote and "clonote"--the ethical use of embryonic stem cells. The New England journal of medicine, 351(3), 209–211. https://doi.org/10.1056/NEJMp048147; Kurjak, A., & Tripalo, A. (2004). The facts and doubts about beginning of the human life and personality. Bosnian journal of basic medical sciences, 4(1), 5–14. https://doi.org/10.17305/bjbms.2004.3453 [6] Vazin, T., & Freed, W. J. (2010). Human embryonic stem cells: derivation, culture, and differentiation: a review. Restorative neurology and neuroscience, 28(4), 589–603. https://doi.org/10.3233/RNN-2010-0543 [7] Socially, at its core, the Western approach to ethics is widely principle-based, autonomy being one of the key factors to ensure a fundamental respect for persons within research. For information regarding autonomy in research, see: Department of Health, Education, and Welfare, & National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1978). The Belmont Report. Ethical principles and guidelines for the protection of human subjects of research.; For a more in-depth review of autonomy within the US, see: Beauchamp, T. L., & Childress, J. F. (1994). Principles of Biomedical Ethics. Oxford University Press. [8] Sherley v. Sebelius, 644 F.3d 388 (D.C. Cir. 2011), citing 45 C.F.R. 46.204(b) and [42 U.S.C. § 289g(b)]. https://www.cadc.uscourts.gov/internet/opinions.nsf/6c690438a9b43dd685257a64004ebf99/$file/11-5241-1391178.pdf [9] Stem Cell Research Enhancement Act of 2005, H. R. 810, 109th Cong. (2001). https://www.govtrack.us/congress/bills/109/hr810/text; Bush, G. W. (2006, July 19). Message to the House of Representatives. National Archives and Records Administration. https://georgewbush-whitehouse.archives.gov/news/releases/2006/07/20060719-5.html [10] National Archives and Records Administration. (2009, March 9). Executive order 13505 -- removing barriers to responsible scientific research involving human stem cells. National Archives and Records Administration. https://obamawhitehouse.archives.gov/the-press-office/removing-barriers-responsible-scientific-research-involving-human-stem-cells [11] Hurlbut, W. B. (2006). Science, Religion, and the Politics of Stem Cells. Social Research, 73(3), 819–834. http://www.jstor.org/stable/40971854 [12] Akpa-Inyang, Francis & Chima, Sylvester. (2021). South African traditional values and beliefs regarding informed consent and limitations of the principle of respect for autonomy in African communities: a cross-cultural qualitative study. BMC Medical Ethics. 22. 10.1186/s12910-021-00678-4. [13] Source for further reading: Tangwa G. B. (2007). Moral status of embryonic stem cells: perspective of an African villager. Bioethics, 21(8), 449–457. https://doi.org/10.1111/j.1467-8519.2007.00582.x , see also Mnisi, F. M. (2020). An African analysis based on ethics of Ubuntu - are human embryonic stem cell patents morally justifiable? African Insight, 49(4). [14] Jecker, N. S., & Atuire, C. (2021). Bioethics in Africa: A contextually enlightened analysis of three cases. Developing World Bioethics, 22(2), 112–122. https://doi.org/10.1111/dewb.12324 [15] Jecker, N. S., & Atuire, C. (2021). Bioethics in Africa: A contextually enlightened analysis of three cases. Developing World Bioethics, 22(2), 112–122. https://doi.org/10.1111/dewb.12324 [16] Jackson, C.S., Pepper, M.S. Opportunities and barriers to establishing a cell therapy programme in South Africa. Stem Cell Res Ther 4, 54 (2013). https://doi.org/10.1186/scrt204; Pew Research Center. (2014, May 1). Public health a major priority in African nations. Pew Research Center’s Global Attitudes Project. https://www.pewresearch.org/global/2014/05/01/public-health-a-major-priority-in-african-nations/ [17] Department of Health Republic of South Africa. (2021). Health Research Priorities (revised) for South Africa 2021-2024. National Health Research Strategy. https://www.health.gov.za/wp-content/uploads/2022/05/National-Health-Research-Priorities-2021-2024.pdf [18] Oosthuizen, H. (2013). Legal and Ethical Issues in Stem Cell Research in South Africa. In: Beran, R. (eds) Legal and Forensic Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-32338-6_80, see also: Gaobotse G (2018) Stem Cell Research in Africa: Legislation and Challenges. J Regen Med 7:1. doi: 10.4172/2325-9620.1000142 [19] United States Bureau of Citizenship and Immigration Services. (1998). Tunisia: Information on the status of Christian conversions in Tunisia. UNHCR Web Archive. https://webarchive.archive.unhcr.org/20230522142618/https://www.refworld.org/docid/3df0be9a2.html [20] Gaobotse, G. (2018) Stem Cell Research in Africa: Legislation and Challenges. J Regen Med 7:1. doi: 10.4172/2325-9620.1000142 [21] Kooli, C. Review of assisted reproduction techniques, laws, and regulations in Muslim countries. Middle East Fertil Soc J 24, 8 (2020). https://doi.org/10.1186/s43043-019-0011-0; Gaobotse, G. (2018) Stem Cell Research in Africa: Legislation and Challenges. J Regen Med 7:1. doi: 10.4172/2325-9620.1000142 [22] Pang M. C. (1999). Protective truthfulness: the Chinese way of safeguarding patients in informed treatment decisions. Journal of medical ethics, 25(3), 247–253. https://doi.org/10.1136/jme.25.3.247 [23] Wang, L., Wang, F., & Zhang, W. (2021). Bioethics in China’s biosecurity law: Forms, effects, and unsettled issues. Journal of law and the biosciences, 8(1). https://doi.org/10.1093/jlb/lsab019 https://academic.oup.com/jlb/article/8/1/lsab019/6299199 [24] Wang, Y., Xue, Y., & Guo, H. D. (2022). Intervention effects of traditional Chinese medicine on stem cell therapy of myocardial infarction. Frontiers in pharmacology, 13, 1013740. https://doi.org/10.3389/fphar.2022.1013740 [25] Li, X.-T., & Zhao, J. (2012). Chapter 4: An Approach to the Nature of Qi in TCM- Qi and Bioenergy. In Recent Advances in Theories and Practice of Chinese Medicine (p. 79). InTech. [26] Luo, D., Xu, Z., Wang, Z., & Ran, W. (2021). China's Stem Cell Research and Knowledge Levels of Medical Practitioners and Students. Stem cells international, 2021, 6667743. https://doi.org/10.1155/2021/6667743 [27] Luo, D., Xu, Z., Wang, Z., & Ran, W. (2021). China's Stem Cell Research and Knowledge Levels of Medical Practitioners and Students. Stem cells international, 2021, 6667743. https://doi.org/10.1155/2021/6667743 [28] Zhang, J. Y. (2017). Lost in translation? accountability and governance of Clinical Stem Cell Research in China. Regenerative Medicine, 12(6), 647–656. https://doi.org/10.2217/rme-2017-0035 [29] Wang, L., Wang, F., & Zhang, W. (2021). Bioethics in China’s biosecurity law: Forms, effects, and unsettled issues. Journal of law and the biosciences, 8(1). https://doi.org/10.1093/jlb/lsab019 https://academic.oup.com/jlb/article/8/1/lsab019/6299199 [30] Chen, H., Wei, T., Wang, H. et al. Association of China’s two-child policy with changes in number of births and birth defects rate, 2008–2017. BMC Public Health 22, 434 (2022). https://doi.org/10.1186/s12889-022-12839-0 [31] Azuma, K. Regulatory Landscape of Regenerative Medicine in Japan. Curr Stem Cell Rep 1, 118–128 (2015). https://doi.org/10.1007/s40778-015-0012-6 [32] Harris, R. (2005, May 19). Researchers Report Advance in Stem Cell Production. NPR. https://www.npr.org/2005/05/19/4658967/researchers-report-advance-in-stem-cell-production [33] Park, S. (2012). South Korea steps up stem-cell work. Nature. https://doi.org/10.1038/nature.2012.10565 [34] Resnik, D. B., Shamoo, A. E., & Krimsky, S. (2006). Fraudulent human embryonic stem cell research in South Korea: lessons learned. Accountability in research, 13(1), 101–109. https://doi.org/10.1080/08989620600634193. [35] Alahmad, G., Aljohani, S., & Najjar, M. F. (2020). Ethical challenges regarding the use of stem cells: interviews with researchers from Saudi Arabia. BMC medical ethics, 21(1), 35. https://doi.org/10.1186/s12910-020-00482-6 [36]Association for the Advancement of Blood and Biotherapies. https://www.aabb.org/regulatory-and-advocacy/regulatory-affairs/regulatory-for-cellular-therapies/international-competent-authorities/saudi-arabia [37] Alahmad, G., Aljohani, S., & Najjar, M. F. (2020). Ethical challenges regarding the use of stem cells: Interviews with researchers from Saudi Arabia. BMC medical ethics, 21(1), 35. https://doi.org/10.1186/s12910-020-00482-6 [38] Alahmad, G., Aljohani, S., & Najjar, M. F. (2020). Ethical challenges regarding the use of stem cells: Interviews with researchers from Saudi Arabia. BMC medical ethics, 21(1), 35. https://doi.org/10.1186/s12910-020-00482-6 Culturally, autonomy practices follow a relational autonomy approach based on a paternalistic deontological health care model. The adherence to strict international research policies and religious pillars within the regulatory environment is a great foundation for research ethics. However, there is a need to develop locally targeted ethics approaches for research (as called for in Alahmad, G., Aljohani, S., & Najjar, M. F. (2020). Ethical challenges regarding the use of stem cells: interviews with researchers from Saudi Arabia. BMC medical ethics, 21(1), 35. https://doi.org/10.1186/s12910-020-00482-6), this decision-making approach may help advise a research decision model. For more on the clinical cultural autonomy approaches, see: Alabdullah, Y. Y., Alzaid, E., Alsaad, S., Alamri, T., Alolayan, S. W., Bah, S., & Aljoudi, A. S. (2022). Autonomy and paternalism in Shared decision‐making in a Saudi Arabian tertiary hospital: A cross‐sectional study. Developing World Bioethics, 23(3), 260–268. https://doi.org/10.1111/dewb.12355; Bukhari, A. A. (2017). Universal Principles of Bioethics and Patient Rights in Saudi Arabia (Doctoral dissertation, Duquesne University). https://dsc.duq.edu/etd/124; Ladha, S., Nakshawani, S. A., Alzaidy, A., & Tarab, B. (2023, October 26). Islam and Bioethics: What We All Need to Know. Columbia University School of Professional Studies. https://sps.columbia.edu/events/islam-and-bioethics-what-we-all-need-know [39] Ababneh, M. A., Al-Azzam, S. I., Alzoubi, K., Rababa’h, A., & Al Demour, S. (2021). Understanding and attitudes of the Jordanian public about clinical research ethics. Research Ethics, 17(2), 228-241. https://doi.org/10.1177/1747016120966779 [40] Ababneh, M. A., Al-Azzam, S. I., Alzoubi, K., Rababa’h, A., & Al Demour, S. (2021). Understanding and attitudes of the Jordanian public about clinical research ethics. Research Ethics, 17(2), 228-241. https://doi.org/10.1177/1747016120966779 [41] Dajani, R. (2014). Jordan’s stem-cell law can guide the Middle East. Nature 510, 189. https://doi.org/10.1038/510189a [42] Dajani, R. (2014). Jordan’s stem-cell law can guide the Middle East. Nature 510, 189. https://doi.org/10.1038/510189a [43] The EU’s definition of autonomy relates to the capacity for creating ideas, moral insight, decisions, and actions without constraint, personal responsibility, and informed consent. However, the EU views autonomy as not completely able to protect individuals and depends on other principles, such as dignity, which “expresses the intrinsic worth and fundamental equality of all human beings.” Rendtorff, J.D., Kemp, P. (2019). Four Ethical Principles in European Bioethics and Biolaw: Autonomy, Dignity, Integrity and Vulnerability. In: Valdés, E., Lecaros, J. (eds) Biolaw and Policy in the Twenty-First Century. International Library of Ethics, Law, and the New Medicine, vol 78. Springer, Cham. https://doi.org/10.1007/978-3-030-05903-3_3 [44] Council of Europe. Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (ETS No. 164) https://www.coe.int/en/web/conventions/full-list?module=treaty-detail&treatynum=164 (forbidding the creation of embryos for research purposes only, and suggests embryos in vitro have protections.); Also see Drabiak-Syed B. K. (2013). New President, New Human Embryonic Stem Cell Research Policy: Comparative International Perspectives and Embryonic Stem Cell Research Laws in France. Biotechnology Law Report, 32(6), 349–356. https://doi.org/10.1089/blr.2013.9865 [45] Rendtorff, J.D., Kemp, P. (2019). Four Ethical Principles in European Bioethics and Biolaw: Autonomy, Dignity, Integrity and Vulnerability. In: Valdés, E., Lecaros, J. (eds) Biolaw and Policy in the Twenty-First Century. International Library of Ethics, Law, and the New Medicine, vol 78. Springer, Cham. https://doi.org/10.1007/978-3-030-05903-3_3 [46] Tomuschat, C., Currie, D. P., Kommers, D. P., & Kerr, R. (Trans.). (1949, May 23). Basic law for the Federal Republic of Germany. https://www.btg-bestellservice.de/pdf/80201000.pdf [47] Regulation of Stem Cell Research in Germany. Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-germany [48] Regulation of Stem Cell Research in Finland. Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-finland [49] Regulation of Stem Cell Research in Spain. Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-spain [50] Some sources to consider regarding ethics models or regulatory oversights of other cultures not covered: Kara MA. Applicability of the principle of respect for autonomy: the perspective of Turkey. J Med Ethics. 2007 Nov;33(11):627-30. doi: 10.1136/jme.2006.017400. PMID: 17971462; PMCID: PMC2598110. Ugarte, O. N., & Acioly, M. A. (2014). The principle of autonomy in Brazil: one needs to discuss it ... Revista do Colegio Brasileiro de Cirurgioes, 41(5), 374–377. https://doi.org/10.1590/0100-69912014005013 Bharadwaj, A., & Glasner, P. E. (2012). Local cells, global science: The rise of embryonic stem cell research in India. Routledge. For further research on specific European countries regarding ethical and regulatory framework, we recommend this database: Regulation of Stem Cell Research in Europe. Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-europe [51] Klitzman, R. (2006). Complications of culture in obtaining informed consent. The American Journal of Bioethics, 6(1), 20–21. https://doi.org/10.1080/15265160500394671 see also: Ekmekci, P. E., & Arda, B. (2017). Interculturalism and Informed Consent: Respecting Cultural Differences without Breaching Human Rights. Cultura (Iasi, Romania), 14(2), 159–172.; For why trust is important in research, see also: Gray, B., Hilder, J., Macdonald, L., Tester, R., Dowell, A., & Stubbe, M. (2017). Are research ethics guidelines culturally competent? Research Ethics, 13(1), 23-41. https://doi.org/10.1177/1747016116650235 [52] The Qur'an (M. Khattab, Trans.). (1965). Al-Mu’minun, 23: 12-14. https://quran.com/23 [53] Lenfest, Y. (2017, December 8). Islam and the beginning of human life. Bill of Health. https://blog.petrieflom.law.harvard.edu/2017/12/08/islam-and-the-beginning-of-human-life/ [54] Aksoy, S. (2005). Making regulations and drawing up legislation in Islamic countries under conditions of uncertainty, with special reference to embryonic stem cell research. Journal of Medical Ethics, 31:399-403.; see also: Mahmoud, Azza. "Islamic Bioethics: National Regulations and Guidelines of Human Stem Cell Research in the Muslim World." Master's thesis, Chapman University, 2022. https://doi.org/10.36837/ chapman.000386 [55] Rashid, R. (2022). When does Ensoulment occur in the Human Foetus. Journal of the British Islamic Medical Association, 12(4). ISSN 2634 8071. https://www.jbima.com/wp-content/uploads/2023/01/2-Ethics-3_-Ensoulment_Rafaqat.pdf. [56] Sivaraman, M. & Noor, S. (2017). Ethics of embryonic stem cell research according to Buddhist, Hindu, Catholic, and Islamic religions: perspective from Malaysia. Asian Biomedicine,8(1) 43-52. https://doi.org/10.5372/1905-7415.0801.260 [57] Jafari, M., Elahi, F., Ozyurt, S. & Wrigley, T. (2007). 4. Religious Perspectives on Embryonic Stem Cell Research. In K. Monroe, R. Miller & J. Tobis (Ed.), Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues (pp. 79-94). Berkeley: University of California Press. https://escholarship.org/content/qt9rj0k7s3/qt9rj0k7s3_noSplash_f9aca2e02c3777c7fb76ea768ba458f0.pdf https://doi.org/10.1525/9780520940994-005 [58] Lecso, P. A. (1991). The Bodhisattva Ideal and Organ Transplantation. Journal of Religion and Health, 30(1), 35–41. http://www.jstor.org/stable/27510629; Bodhisattva, S. (n.d.). The Key of Becoming a Bodhisattva. A Guide to the Bodhisattva Way of Life. http://www.buddhism.org/Sutras/2/BodhisattvaWay.htm [59] There is no explicit religious reference to when life begins or how to conduct research that interacts with the concept of life. However, these are relevant verses pertaining to how the fetus is viewed. ((King James Bible. (1999). Oxford University Press. (original work published 1769)) Jerimiah 1: 5 “Before I formed thee in the belly I knew thee; and before thou camest forth out of the womb I sanctified thee…” In prophet Jerimiah’s insight, God set him apart as a person known before childbirth, a theme carried within the Psalm of David. Psalm 139: 13-14 “…Thou hast covered me in my mother's womb. I will praise thee; for I am fearfully and wonderfully made…” These verses demonstrate David’s respect for God as an entity that would know of all man’s thoughts and doings even before birth. [60] It should be noted that abortion is not supported as well. [61] The Vatican. (1987, February 22). Instruction on Respect for Human Life in Its Origin and on the Dignity of Procreation Replies to Certain Questions of the Day. Congregation For the Doctrine of the Faith. https://www.vatican.va/roman_curia/congregations/cfaith/documents/rc_con_cfaith_doc_19870222_respect-for-human-life_en.html [62] The Vatican. (2000, August 25). Declaration On the Production and the Scientific and Therapeutic Use of Human Embryonic Stem Cells. Pontifical Academy for Life. https://www.vatican.va/roman_curia/pontifical_academies/acdlife/documents/rc_pa_acdlife_doc_20000824_cellule-staminali_en.html; Ohara, N. (2003). Ethical Consideration of Experimentation Using Living Human Embryos: The Catholic Church’s Position on Human Embryonic Stem Cell Research and Human Cloning. Department of Obstetrics and Gynecology. Retrieved from https://article.imrpress.com/journal/CEOG/30/2-3/pii/2003018/77-81.pdf. [63] Smith, G. A. (2022, May 23). Like Americans overall, Catholics vary in their abortion views, with regular mass attenders most opposed. Pew Research Center. https://www.pewresearch.org/short-reads/2022/05/23/like-americans-overall-catholics-vary-in-their-abortion-views-with-regular-mass-attenders-most-opposed/ [64] Rosner, F., & Reichman, E. (2002). Embryonic stem cell research in Jewish law. Journal of halacha and contemporary society, (43), 49–68.; Jafari, M., Elahi, F., Ozyurt, S. & Wrigley, T. (2007). 4. Religious Perspectives on Embryonic Stem Cell Research. In K. Monroe, R. Miller & J. Tobis (Ed.), Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues (pp. 79-94). Berkeley: University of California Press. https://escholarship.org/content/qt9rj0k7s3/qt9rj0k7s3_noSplash_f9aca2e02c3777c7fb76ea768ba458f0.pdf https://doi.org/10.1525/9780520940994-005 [65] Schenker J. G. (2008). The beginning of human life: status of embryo. Perspectives in Halakha (Jewish Religious Law). Journal of assisted reproduction and genetics, 25(6), 271–276. https://doi.org/10.1007/s10815-008-9221-6 [66] Ruttenberg, D. (2020, May 5). The Torah of Abortion Justice (annotated source sheet). Sefaria. https://www.sefaria.org/sheets/234926.7?lang=bi&with=all&lang2=en [67] Jafari, M., Elahi, F., Ozyurt, S. & Wrigley, T. (2007). 4. Religious Perspectives on Embryonic Stem Cell Research. In K. Monroe, R. Miller & J. Tobis (Ed.), Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues (pp. 79-94). Berkeley: University of California Press. https://escholarship.org/content/qt9rj0k7s3/qt9rj0k7s3_noSplash_f9aca2e02c3777c7fb76ea768ba458f0.pdf https://doi.org/10.1525/9780520940994-005 [68] Gert, B. (2007). Common morality: Deciding what to do. Oxford Univ. Press. [69] World Medical Association (2013). World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA, 310(20), 2191–2194. https://doi.org/10.1001/jama.2013.281053 Declaration of Helsinki – WMA – The World Medical Association.; see also: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. (1979). The Belmont report: Ethical principles and guidelines for the protection of human subjects of research. U.S. Department of Health and Human Services. https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html [70] Zakarin Safier, L., Gumer, A., Kline, M., Egli, D., & Sauer, M. V. (2018). Compensating human subjects providing oocytes for stem cell research: 9-year experience and outcomes. Journal of assisted reproduction and genetics, 35(7), 1219–1225. https://doi.org/10.1007/s10815-018-1171-z https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063839/ see also: Riordan, N. H., & Paz Rodríguez, J. (2021). Addressing concerns regarding associated costs, transparency, and integrity of research in recent stem cell trial. Stem Cells Translational Medicine, 10(12), 1715–1716. https://doi.org/10.1002/sctm.21-0234 [71] Klitzman, R., & Sauer, M. V. (2009). Payment of egg donors in stem cell research in the USA. Reproductive biomedicine online, 18(5), 603–608. https://doi.org/10.1016/s1472-6483(10)60002-8 [72] Krosin, M. T., Klitzman, R., Levin, B., Cheng, J., & Ranney, M. L. (2006). Problems in comprehension of informed consent in rural and peri-urban Mali, West Africa. Clinical trials (London, England), 3(3), 306–313. https://doi.org/10.1191/1740774506cn150oa [73] Veatch, Robert M. Hippocratic, Religious, and Secular Medical Ethics: The Points of Conflict. Georgetown University Press, 2012. [74] Msoroka, M. S., & Amundsen, D. (2018). One size fits not quite all: Universal research ethics with diversity. Research Ethics, 14(3), 1-17. https://doi.org/10.1177/1747016117739939 [75] Pirzada, N. (2022). The Expansion of Turkey’s Medical Tourism Industry. Voices in Bioethics, 8. https://doi.org/10.52214/vib.v8i.9894 [76] Stem Cell Tourism: False Hope for Real Money. Harvard Stem Cell Institute (HSCI). (2023). https://hsci.harvard.edu/stem-cell-tourism, See also: Bissassar, M. (2017). Transnational Stem Cell Tourism: An ethical analysis. Voices in Bioethics, 3. https://doi.org/10.7916/vib.v3i.6027 [77]Song, P. (2011) The proliferation of stem cell therapies in post-Mao China: problematizing ethical regulation, New Genetics and Society, 30:2, 141-153, DOI: 10.1080/14636778.2011.574375 [78] Dajani, R. (2014). Jordan’s stem-cell law can guide the Middle East. Nature 510, 189. https://doi.org/10.1038/510189a [79] International Society for Stem Cell Research. (2024). Standards in stem cell research. International Society for Stem Cell Research. https://www.isscr.org/guidelines/5-standards-in-stem-cell-research [80] Benjamin, R. (2013). People’s science bodies and rights on the Stem Cell Frontier. Stanford University Press.

Photo ID 131102170 © Geckophotos | Dreamstime.com INTRODUCTION Medical tourism should contribute to developing a more robust healthcare system that acts in the best interests of patients and ensures equal access to healthcare. This paper examines medical tourism in Colombia and argues that developing a system that aligns with bioethical principles is necessary. People traveling for care should have access to the Ministry of Health rather than only the Ministry of Industry and Tourism, emphasizing their purpose as patients seeking medical procedures or treatments rather than tourists engaging in leisure activities. Additionally, in the interest of justice, Colombian patients should benefit from the revenue derived from medical tourism. It is crucial to recognize that both patients traveling for care and people in the destination country can derive benefits from medical tourism. The Colombian government can protect the rights and well-being of patients seeking care and ensure that any benefits are distributed fairly among Colombian citizens. I. Background Medical tourism refers to people traveling to foreign countries to obtain health care.[1] Many individuals from high-income countries seek health care in less developed countries to take advantage of the lower costs. Destination countries are increasingly showing interest in becoming medical tourism hubs due to the significant financial potential of this multi-billion dollar industry. The global medical tourism market is projected to reach $207.9 billion by 2027.[2] This growth not only generates income but also creates employment opportunities and business prospects for local residents in sectors such as tourism, pharmaceuticals, and infrastructure. By establishing themselves as medical tourism destinations, countries can stimulate economic development and enhance their healthcare structure. Colombia is among the fastest-growing medical tourism destinations in the world. It has become a popular destination for medical tourists due to its advanced healthcare infrastructure, biotechnology, and highly skilled physicians who cater to international patients at affordable prices.[3] The healthcare entities in Colombia offer a wide range of medical procedures, including cardiovascular, bariatric, orthopedics, cosmetic surgery, dental care, and fertility treatments. [4] The Colombian government has actively promoted medical tourism to position the country as a destination for world-class medical services.[5] Through strategic economic policies, effective regulation, and digital marketing, medical tourism has emerged as a significant contributor to Colombia’s income. The Colombian Ministry of Industry and Tourism, which regulates medical tourism in Colombia, forecasts at least 2.8 million health tourists and a revenue of at least $6.3 billion by 2032.[6] Colombia intends to have medical tourism play a significant role in its economy. However, ethical issues exist. The Colombia Ministry of Industry and Tourism is more involved in medical tourism than the Ministry of Health is. Additionally, the government has not been held accountable for the shortcomings in the medical tourism industry. There should be an organization advocating for the rights and well-being of medical tourists. Furthermore, using public funds to attract international patients may divert funds from local communities. Last, the negative impacts of medical tourism on Colombian patients deserve attention. This paper aims to explore these ethical issues from two perspectives: that of medical tourists and that of Colombian citizens. I argue that the benefits of medical tourism outweigh the harms but that those traveling for health care deserve protection. II. Patients: Are They International Patients or Tourists? When medical tourists seek hospitals and physicians in a destination country, facilitators may direct them to non-licensed practitioners and questionable facilities. These facilitators, who receive commissions, may not act in the patient’s best interest. Rather, like travel agents, they base their referrals on the referral fees that hospitals or physicians pay.[7] International patients risk getting lower-quality health care from unregulated hospitals or providers. This can interfere with informed consent and increase the risk of infections. There may be an absence of medical malpractice coverage from physicians. Unregulated or unlicensed medical care may even lead to patient fatalities. Therefore, it is crucial for international patients to carefully evaluate the risks associated with “booking” their healthcare options. To mitigate these risks, it is important for international patients to thoroughly assess the accreditation status of the hospital or clinic they plan to visit. The Joint Commission International (JCI) accreditation can provide patients with an external quality assessment and assist them in making an informed decision.[8] International patients should proactively seek out certified and reputable healthcare providers and institutions to ensure both their safety and a high quality of care. Colombia has five hospitals and clinics with JCI accreditation.[9] Colombia is the third most-used destination for plastic surgery in the world; the first is Brazil, and the second is Turkey. In Colombia, one out of every three plastic surgery patients is an international patient.[10] The Colombian Association for Plastic Surgery advises all patients to check the hospital's accreditation. Patients should check the website of the local Secretary of Health in each city and see if the physician conducting the plastic surgery is listed.[11] Institutions and doctors must fully comply with requirements, including describing the procedure and obtaining informed consent from patients. It is very common to read in the media plastic surgeries conducted in what is known in Latin America as “clinicas de garage” (garage clinics) with negative results and deaths.[12] Official data covers plastic surgeries conducted at accredited institutions with registered doctors. There is a lack of data on garage clinics. There are a few things the government can do to make medical tourism safer. First, the Ministry of Health’s website should maintain a list of healthcare providers with JCI accreditation. In each city, the local Secretary of Health is responsible for providing patients with information about the quality of care of the hospitals in its region. Second, the government should take responsibility for providing accurate and comprehensive information to international patients, enabling them to make fully informed decisions regarding their medical procedures. In the context of informed consent, patients may have trouble understanding due to language barriers, terminology, and the complexity of the risks involved in medical procedures. Lastly, Congress should enact a legal framework that determines the responsibility of all parties involved in medical tourism.[13] In the unfortunate event that a medical tourist requires intensive care, it becomes imperative to determine who will bear the responsibility for their well-being and any potential financial implications. Medical tourists are not protected from errors and failures of medical procedures because the Colombia Constitution specifies that the healthcare system exclusively caters to its citizens, while coverage for foreigners is limited to emergencies only. The US State Department recommends that those traveling to Colombia have international health insurance.[14] International patients can sue doctors in Colombia for medical malpractice, referred to as medical liability.[15] The government should take responsibility for certifying medical institutions and issuing medical visas with specific requirements and regulations specific to medical tourism.[16] A new medical visa system is in place. Changing the terminology may help the government see those traveling for care as medical patients rather than medical tourists. That may lead to a different mindset and spur the government to protect them and ensure high-quality care. It may also help those traveling avoid tourism industry facilitators and find reputable surgeons and hospitals. III. Are Colombian Patients and the Local Healthcare System Benefiting from Medical Tourism? The main reason for the growth of medical tourism from developed countries to developing countries like Colombia is the excessive cost of treatment in wealthier nations.[17] Other reasons include the long queues for certain types of medical services in the home country, the availability of better technologies abroad, inadequate (or absence of) health insurance, and the unavailability[18] (or prohibition) of certain medical services in the home country.[19] The Colombian Constitution recognizes health as a fundamental right for all citizens.[20] Pursuant to the Constitution’s health mandate, Colombia designed a mandatory universal social health insurance system in 1993. It aims to achieve a fair distribution of resources, opportunities, and services while holding the government accountable.[21] Before 1993, less than 25 percent of the population had coverage; now, between 94 and 99 percent have it, regardless of income level or employment.[22] However, universal care does not entitle Colombian citizens to many of the modern surgical centers, technology, and doctors that tourists access. Local wealthy Colombian citizens tend to purchase private insurance that allows them many more healthcare options.[23] The OECD reports that only 41 percent of Colombian citizens were satisfied with the availability of the quality of care, while the OECD average is 67 percent. According to the OECD, the out-of-pocket health expenditure in Colombia is 14 percent, which is lower than the OECD average of 18 percent. Despite its recognized right to health care, the current system is not providing the quality of care that the people would prefer. Those traveling to Colombia for care are not covered by universal social health insurance and must pay for their health care[24] out of pocket or through their private insurers using international coverage.[25] Like local supplemental private insurance, medical tourists and their insurance plans tend to pay more for their care than the rate that the universal system would pay the providers for care provided to the general Colombian population. This situation often leads to higher revenue from medical tourists than local patients unless the local patients have supplemental private insurance. The mismatched payment schemes leave the local population with unequal access to healthcare resources[26] since healthcare providers prefer to cater to patients paying more than the government-subsidized insurance pays. Medical tourism “threatens to result in a dual market structure”[27] characterized by a higher-quality, expensive segment that serves wealthy nationals and foreigners alongside a lower-quality segment that caters to the poor, most of whom are covered by universal healthcare coverage.[28] Medical tourists should pay taxes or a special premium to improve the local healthcare system. While the medical tourism industry arguably generates tax revenue,[29] some additional money should flow from the medical tourists to the healthcare outlets that the local people use. Then, the country can benefit even more from promoting medical tourism while ensuring that the government and the healthcare system follow the principles of justice, beneficence, and public welfare.[30] In Colombia, Fundación Cardioinfantil, a private non-profit hospital known as “La Cardio,” is a good example of a regional leader committed to providing clinical excellence to both national and international patients.[31] About 20 years ago, La Cardio, well known for its cardiovascular health care, aimed to become the top hospital in the region (Latin America and the Caribbean) to obtain financial resources for improving its facilities. It became the first hospital in Colombia to achieve the JCI accreditation, attracting patients from countries with inadequate cardiovascular healthcare systems.[32] Foreign governments covered their citizens’ medical expenses, allowing La Cardio to fund system improvement. Currently ranked as the fifth-best clinic in Latin America and having won the Gold Award for Corporate Social Responsibility, La Cardio has received recognition for its dedication to serving economically disadvantaged Colombian patients.[33] This example demonstrates how introducing a high-paying market has not led to neglecting local patients, as resources from medical tourists are used to enhance the healthcare system for the local population. CONCLUSION The Colombian government needs to recognize that international patients are seeking medical services, not tourism or vacation experiences. Therefore, a new policy should categorize international patients separately from the tourism sector and treat them purely as patients. The introduction of medical visas may help this. Once establishing international patients are patients and not tourists, the Colombian government could impose taxes on them and allocate the funds generated to reinvest in the healthcare needs of its citizens, ensuring justice and promoting awareness of the ethical rights of international patients. At the same time, home country governments directing patients to a destination country should conduct thorough due diligence of the ethical principles applied to international patients as well as the accreditation of the destination country’s hospitals. Colombia may be aware of the implications of the difference in terms but unwilling to modify the language due to the associated costs, liabilities, and risks involved. - [1] Gaines, J., Lee, C. V. (2019). Medical tourism. Travel Medicine, 371–375. https://doi.org/10.1016/b978-0-323-54696-6.00039-2 https://www.sciencedirect.com/science/article/pii/B9780323546966000392 [2] Forecasted Evolution of Medical Travels, 2023-2027: A Segmental View. ReportLinker. (2023, December). https://www.reportlinker.com/p06473784/Medical-Tourism-Market-Size-Share-Trends-and-Analysis-by-Region-Service-Provider-and-Segment-Forecast.html [3] Forecasted Evolution of Medical Travels, 2023-2027: A Segmental View. ReportLinker. (2023, December). [4] Arias-Aragonés, F.J.A., Payares, A.M.C., & Jiménez, O.J. (2020). Characterization of the healthcare tourism in the city of Bogotá and the District of Cartagena. Clío América, 14 (28), 486-492. https://doi.org/10.21676/23897848.3941 [5] Arias-Aragonés, et al. (2020). [6] Arias- Aragones, et al. (2020). https://www.colombiaproductiva.com/ptp-sectores/historico/turismo-salud (citing the Colombian Production Transformation Program (PTP)) [7] Glenn Cohen, Patients with Passports Medical Tourism, Law, and Ethics. New York Oxford University Press, 2015, p. 25 [8] Glenn, Cohen. (2015), p. 23-24. [9] A Global Leader for Health Care Quality and Patient Safety. Joint Commission International. https://www.jointcommissioninternational.org/ (The five Colombian hospitals and clinics with JCI accreditation are two hospitals in the capital city Bogota (la Cardio and Fundación Hospital Universitario Santa Fé de Bogotá), one hospital in Cali (Clinica Inbanaco), one hospital in Medellín (Hospital Pablo Tobón), and one clinic in Florida Blanca (Fundación Cardiovascular de Colombia). Nearby countries such as Venezuela and Trinidad Tobago do not have any accredited hospitals or clinics. Ecuador and Panamá have one each, Perú has eleven, and Brazil has seventy-one.) [10] International Society of Aesthetic Plastic Surgery ISAPS (2023), ISAPS International Survey on Aesthetic/Cosmetic Procedures performed in 2022, p. 52. https://www.isaps.org/discover/about-isaps/global-statistics/reports-and-press-releases/global-survey-2022-full-report-and-press-releases/ (most frequently cited countries of foreign patients in Colombia are the US, Spain, and Panama.) [11] Why choose a member of the SCCP. (2023). Colombia Plastic Surgery Association (SCCP). https://cirugiaplastica.org.co/porque-elegir-un-miembro-de-la-sccp/ See also: To Find a Surgeon. (2023). Colombia Plastic Surgery Association (SCCP). https://cirugiaplastica.org.co (This website is helpful for checking the list of members of the SCCP.) [12] Cosmetic Surgeries Performed in Garage Offices can Become a Public Health Problem. Concejo de Bogotá D.C. (2022). https://concejodebogota.gov.co/cirugias-esteticas-practicadas-en-consultorios-de-garaje-se-pueden/cbogota/2015-07-17/100100.php (There are many cases of deaths resulting from illegal plastic surgeries. The local government in Bogota is aware of the deaths, as reported in the Bogota Counsel (2015)). See also Travel.State.Gov, US Department of State, Bureau of Consular Affairs. (August 17, 2023). https://travel.state.gov/content/travel/en/international-travel/International-Travel-Country-Information-Pages/Colombia.html (There is a warning that says: “Although Colombia has many elective/cosmetic surgery facilities that are on par with those found in the United States, the quality of care varies widely. If you plan to undergo surgery in Colombia, carefully research the doctor and recovery facility you plan to use. Make sure that emergency medical facilities are available, and that professionals are accredited and qualified. Share all health information (e.g., medical conditions, medications, allergies) with your doctor before surgery.") [13] Arias-Aragonés, F.J.A., Payares, A.M.C., & Jiménez, O.J. (2020), p. 490. (report “the absence of regulation and a legal framework that determines the responsibilities of each link in the production chain” as a difficulty that affects competitivity to become a leader in medical tourism in the Latin American region.) See also: Trujillo, M. A. (2023, November 24). Colombia’s New Bill on Regulating Cosmetic Surgeries. BNN Breaking. https://bnn.network/breaking-news/health/colombia-to-regulate-cosmetic-surgeries-a-step-towards-patient-safety/ (On November 22, 2023, as a response to rising cases of death and injuries associated with plastic surgeries, a bill was introduced in the Colombian House of Representatives to regulate the practice of cosmetic surgeries and protect the integrity of patients) [14] U.S. Department of State, Travel.State.Gov, Colombia. (August 17, 2023). Traveler’s Checklist, https://travel.state.gov/content/travel/en/international-travel/International-Travel-Country-Information-Pages/Colombia.html [15] U.S. Department of State, Travel.State.Gov, Colombia. (August 17, 2023). Traveler’s Checklist. See also: Medical Tourism and Elective Surgery. The Department of State informs that “U.S. citizens have suffered serious complications or died during or after having cosmetic surgery or other elective surgery“ and “the legal options in cases of malpractice are very limited in Colombia,” https://travel.state.gov/content/travel/en/international-travel/International-Travel-Country-Information-Pages/Colombia.html See also: The law firm Alvarez Gonzalez Tolosa Attorneys. (August 8, 2023). Medical Malpractice in Colombia, includes medical malpractice as one of the areas of expertise of the firm. https://www.agtattorneys.com/blog/medical-malpractice-in-colombia/ [16] Colombia recently enacted a new visa regulation (Resolution 5477 from July 22, 2022, issued by the Ministry of Foreign Affairs) effective as of October 22, 2022. No data currently exists about a "medical treatment" visa because it is a new legislation. Even though the regulation refers to the visitor as a patient and includes requirements such as (1) a letter from the medical institution explaining the treatment and approximate duration, (2) a letter explaining costs and who will pay for the treatment, (3) insurance policy, and (4) the general requirements for tourists, the regulation specifically explains that this kind of visa is considered as a TOURISM visa (art 37). [17] Glenn, Cohen. 2015 [18] Frequently Asked Questions. Bioxcellerator. https://www.bioxcellerator.com/faqs (For example, Bioxellerator stem cell therapies conducted in Medellin, Colombia, are not FDA-approved.) [19] Vovk, Viktoriia, Lyudmila Beztelesna, and Olha Pliashko. (2021). "Identification of Factors for the Development of Medical Tourism in the World" International Journal of Environmental Research and Public Health 18, no. 21: 11205. https://doi.org/10.3390/ijerph182111205 [20] Colombian Constitution. (1991). art. 49 [21] Ministry of Health and Protection. Columbia Ministry of Health. (2023). https://www.minsalud.gov.co/English/Paginas/Ministry.aspx [22] “Does Colombia’s Health System Need an Overhaul?” (March 2, 2023). The Dialogue, Latin America Advisor. https://www.thedialogue.org/analysis/does-colombias-health-system-need-an-overhaul/ [23] Health at a Glance 2021 Colombia Country Note. OECD. (2023). https://search.oecd.org/colombia/health-at-a-glance-Colombia-EN.pdf [24] Travel.State.Gov, US Department of State, Bureau of Consular Affairs. https://travel.state.gov/content/travel/en/international-travel/International-Travel-Country-Information-Pages/Colombia.html [25] Glenn, Cohen. (2015). p. 2-9. [26] Banco de la República. (2023). Regional Health Inequalities in Colombia. https://www.banrep.gov.co/en/regional-health-inequalities-colombia (The Central Bank of Colombia (“Banco de la República”) in reports that despite having relatively high health coverage compared with other countries, empirical results show persistent inequalities in the healthcare system. The aim is to reduce and eventually eliminate such inequalities.) [27] Glenn, Cohen (2015), p. 158-160, citing Rupa Chanda, an Indian business professor, Trade in Health Services, 80 Bull. World Health Org. 158, 160 (2002). [28] Banco de la República. (2023). Regional Health Inequalities in Columbia. https://investiga.banrep.gov.co/es/be-1233. (Under Colombian law, it is mandatory for all employees and employers to pay 4 percent and 8 percent of the applicable salary, respectively, to the universal healthcare system (EPS) to obtain coverage for the employee and family members. This is known as the contributive system, and the funding is known as parafiscal. The unemployed obtain coverage through the government-subsidized system known as SISBEN (System of Identification of Beneficiaries of Social programs), funded with taxpayers’ money, known as fiscal funding. According to the Central Bank of Colombia (Banco de la República), “in recent years, the healthcare sector has faced financial and administrative problems that have increased the need for fiscal resources for its financing and that could affect its sustainability. Regarding the composition of the outflow, it is worth noting the cost of ensuring the contributory and subsidized regime, which on average explains 80 percent of the total system expenses during the period 2011-2022.” “Additionally, pressures derived from the Covid-19 pandemic, Venezuelan migration” and expenses derived from the increase in the subsidized system due to the high rate of unemployment and informal employment are negatively impacting financing of the healthcare system in Colombia. Additional fiscal resources are needed because the health care Colombians receive costs more than what beneficiaries pay.) [29] Statista. (2023). Revenue of the medical tourism sector in Colombia from 2019 to 2024 https://www.statista.com/statistics/1156551/colombia-revenue-medical-tourism/ [30] Glenn, Cohen. (2015), p.218 (The beneficence principle is the general moral obligation to act for the benefit of others, and some of those acts are obligatory, as is the government’s obligation concerning healthcare.) [31] Hospital Cardioinfantil Bogotá, Colombia. https://cardioinfantil.org [32] Hospital Cardioinfantil https://cardioinfantil.org (Trinidad and Tobago, Aruba, Curacao, and Panamá were the first countries with international agreements with La Cardio.) [33] Hospital Cardioinfantil Bogotá, Colombia. https://www.lacardio.org/historia/