Ethical Issues Resulting from Genetic Technology

Genetic tests are laboratory procedures that identify changes in our genes. Most human disease results, in whole or in part, from alterations in genes. Because the tests are expected to have incredible predictive power and because they may tell us personal information before we are ready to receive it, testing requested by a third party could be considered an infringement on privacy. Furthermore, the technology is new and thus subject to errors in interpretation that could result in unfair discrimination against the person who has been tested. Genes are inherited and are found not only in a single individual but also in some blood relatives. A genetic test therefore involves many people and invades the privacy of all. This paper questions the right of insurers to demand genetic tests but notes that by concealing the results of tests, applicants may practice adverse selection. If ethics are rules of conduct that society requires, then insurers will need to reexamine their ethical responsibilities in the light of this new technology.     

Adult Polycystic Kidney Disease and Insurance

Abstract

Adult Polycystic Kidney Disease (APKD) is a single-gene autosomal dominant genetic disorder leading to end-stage renal disease (ESRD, meaning kidney failure). It is associated with mutations in either of two genes, APKD1 and APKD2, and although diagnosis is still mostly by ultrasonography rather than DNA-based tests, this may change in the future. Recent studies have shown that the rates of onset of ESRD associated with APKD1 mutations are much greater than those associated with APKD2 mutations, a form of genetic heterogeneity that differs from, for example, familial breast cancer. In this paper we model the the impact of mutations in APKD1 or APKD2 on critical illness insurance, extending the work of Gutiérrez and Macdonald (2003), which was based on studies predating DNA-based tests. We then extend the model to life insurance and show that the financial impact is strongly dependent on the availability of treatment (dialysis and transplant), but that if it is available, extra premiums for life insurance are modest. We show that genetic heterogeneity introduces a novel problem, because carrying an APKD2 mutation is less risky than having a family history of APKD. Thus, in jurisdictions where family history may be used in underwriting but genetic tests may not, it may be illegal to use knowledge that benefits the applicant.     

Gene-environment interactions and the complexity of human genetic diseases

In the assessment of mortality and morbidity risk, the ability of family history and genetic test results to predict the age of occurrence, severity, and long-term prognosis of 'genetic' diseases is important. An increasing number of gene-gene and gene-environment interactions have been demonstrated in a number of monogenic Mendelian diseases. These interactions can significantly modify the clinical presentation (disease phenotype) of diseases previously regarded purely as 'genetic.' As a result, 'genetic' diseases can be positioned in a continuum between classic Mendelian and complex disease where the extremes, pure genetic or solely non-genetic, do not exist. The position of any given disease in this continuum is defined by three components: the major gene(s) contributing to the phenotype, the variability added by modifier genes and the significance of environmental factors influencing the phenotype. As the predictive value of genetic test results can be significantly influenced by additional genetic and environmental risk factors, a better understanding of these factors may influence the quantification of mortality and morbidity risk.     

Financial development and barriers to the cross-border diffusion of financial innovation

This paper explores the determinants of financial development by focusing on the role played by barriers to the diffusion of financial technology. These barriers are measured using human genetic distance from the technology frontier. The results based on cross-sectional data for 123 countries suggest that genetic distance to the global frontier has an economically and statistically significant effect on financial development, in that countries that are genetically far from the technology leader tend to have lower levels of financial development. Genetic distance is found to have the largest effect, even after controlling for other determinants of financial development established in the literature. These findings indicate that cultural barriers to the diffusion of financial technology across borders impact financial development by influencing the follower countries’ ability to adopt and adapt innovations from the frontier.     

Relative Hedging of Systematic Mortality Risk

A number of problematic issues have arisen in anticipation of the potential role of molecular tests for genetic predispositions to illness in risk assessment by insurance underwriters. We argue in this paper that the regrettable history and current risks of genetic discrimination warrant a presumption that genetic predisposition status should not be used in any nonmedical contexts, unless compelling evidence can demonstrate that serious harm will result to third-party interests without such use. We argue that insurers should not be able to initiate testing for genetic predisposition. We also argue that there are many reasons to doubt whether patients’ test results will result in such serious adverse selection as to cause substantial harm to insurance markets, except possibly at higher policy amounts in life or disability income insurance. We conclude that the burden of proof must be on insurers to demonstrate necessity of use in specific cases in which test availability shows high probability of imminent, serious harm to insurance markets.     

Genetic testing: affected parties and decision making

The network of issues around information obtained from genetic testing is wide and complex. While risk assessment, awareness and discussion are often public driven, and in many instances, including that of nuclear power, are allied with democratic principles, the case of gene technology and genetic testing appears to be different. The opportunity for risk assessment by gene testing is rejected by many, and this rejection is supported by the claim of the right not to know. This article discusses the background to this development, and argues that decisions that consider issues related to genetic testing should be taken with the participation of affected parties.     

Langlebigkeit und Altern: Gene oder Umwelt?

Aging is defined as loss of homeostasis which affects all metabolic systems, including DNA. Interspecies comparisons and lessons from the human genetic instability syndromes suggest a correlation between DNA-homeostasis and maximum lifespan, whereas average lifespan depends mainly on environmental factors. Current demographic data suggest a maximum lifespan in humans of 110–115. The average life expectancy at birth has reached 80 years in the wealthy nations and may exceed, at least in females, 90 years by the year 2050. Genetic and biological reasons, but also lifestyle factors, account for the greater longevity of women. Attempt to define a ?longevity“ genotype so far have not been met with success, but carriers of the ApoE4-Allele appear to have a disadvantage. Unlike the situation in model organisms, aging and longevity in humans seem to be influenced by numerous genes and environmental interactions. Most people do not die of old age but of age-related diseases which are frequent because of lack of natural selection against genetic defects that cause late-onset diseases. Moreover, genes causing late-onset diseases show evidence of antagonistic pleiotropy, rendering these genes resistant to removal from our genome. Likewise, thermoinstability of DNA and generation of reactive oxygen species during oxidative phosphorylation are two endogenous sources of genomic instability that limit our lifespan and cannot be overcome without fundamentally altering the biological make-up of our species. Genomic instability causes cancer and accelerates the aging process, as evidenced by the human caretaker gene syndromes which typically show progeroid features. From a genetic point of view, cancer and aging may be moderately delayed and / or mitigated by lifestyle and medical / environmental interventions, but given the constraints of our biological make-up, they cannot be eradicated.     

How Genes Modulate Patterns of Aging-Related Changes on the Way to 100: Biodemographic Models and Methods in Genetic Analyses of Longitudinal Data

In this article we clarify mechanisms of genetic regulation of human aging and longevity traits. The objective of this article is to address the issues in previous research of not reaching a genome-wide level of statistical significance and lack of replication in the studies of independent populations. We performed GWAS of human life span using different subsets of data from the original Framingham Heart Study cohort corresponding to different quality control procedures, and we used one subset of selected genetic variants for further analyses. We used a simulation study to show that this approach to combining data improves the quality of GWAS with FHS longitudinal data to compare average age trajectories of physiological variables in carriers and noncarriers of selected genetic variants. We used a stochastic process model of human mortality and aging to investigate genetic influence on hidden biomarkers of aging and on dynamic interaction between aging and longevity. We investigated properties of genes related to selected variants and their roles in signaling and metabolic pathways and showed that the use of different quality control procedures results in different sets of genetic variants associated with life span. We selected 24 genetic variants negatively associated with life span and showed that the joint analyses of genetic data at the time of biospecimen collection and follow-up data substantially improved significance of associations of 24 selected SNPs with life span. We also showed that aging-related changes in physiological variables and in hidden biomarkers of aging differ for the groups of carriers and noncarriers of selected variants. The results of these analyses demonstrated benefits of using biodemographic models and methods in genetic association studies of these traits. Our findings showed that the absence of a large number of genetic variants with deleterious effects may make substantial contribution to exceptional longevity. These effects are dynamically mediated by a number of physiological variables and hidden biomarkers of aging. The results of these research demonstrated benefits of using integrative statistical models of mortality risks in genetic studies of human aging and longevity.     

Frontiers of commercial biotechnology: US and Japanese potential in a new industry

With their godlike ability to alter life and cure disease, the new biotechnologies have moved swiftly out of the laboratory and into various scientific and commercial applications. The small, innovative biotechnology firm has been the principal vehicle for the transition and it has been resoundingly supported by US venture capital and equity markets. Wall Street's support, however, could quickly evaporate, especially if major advances against cancer and AIDS are not soon forthcoming. With increasing Japanese interest in this field, there could be major industrial changes at the frontiers of commercial biotechnology.     

COVID-19 and Inequalities*

This paper brings together evidence from various data sources and the most recent studies to describe what we know so far about the impacts of the COVID-19 crisis on inequalities across several key domains of life, including employment and ability to earn, family life and health. We show how these new fissures interact with existing inequalities along various key dimensions, including socio-economic status, education, age, gender, ethnicity and geography. We find that the deep underlying inequalities and policy challenges that we already had are crucial in understanding the complex impacts of the pandemic itself and our response to it, and that the crisis does in itself have the potential to exacerbate some of these pre-existing inequalities fairly directly. Moreover, it seems likely that the current crisis will leave legacies that will impact inequalities in the long term. These possibilities are not all disequalising, but many are.     

Modeling the Impact of Genetics on Insurance

The role of probabilistic models in the debate over genetics and insurance is discussed. A Markov model is used to show that, under quite extreme assumptions, adverse selection in life insurance ought to be controllable. The statistical problems of estimating small differences in mortality are discussed; these might limit the use of many genetic disorders as rating factors. The influence of the insurance industry on policy-making, especially through its support of research, is discussed. It is suggested that participating contracts are suitable and simple vehicles to carry the genetic risks in life insurance.     

Welfare Effects of Banning Genetic Information in the Life Insurance Market: The Case of BRCA1/2 Genes

We investigate whether regulations that ban insurance companies from access to individuals' genetic tests are likely to lead to substantial adverse selection costs for the specific example of the so‐called breast cancer (BRCA1/2) genes. Using a data set including economic, demographic, and relevant family background information to simulate the market for 10‐year term life insurance, we find generally only modest adverse selection costs associated with such a regulatory ban. However, for family background groups that are at high risk for carrying one of these genes, the efficiency cost of adverse selection may be significant should the test become widely adopted.     

Adult Polycystic Kidney Disease and Critical Illness Insurance

Abstract

Adult polycystic kidney disease (APKD) is a single-gene autosomal dominant genetic disorder leading to end-stage renal disease (ESRD, meaning kidney failure). It is associated with mutations in at least two genes, APKD1 and APKD2, but diagnosis is mostly by ultrasonography. We propose a model for critical illness (CI) insurance and estimate rates of onset of ESRD from APKD using two studies. Other events leading to claims under CI policies are included in the model, which we use to study (a) extra premiums under CI policies if the presence of an APKD mutation is known, and (b) the possible costs arising from adverse selection if this information is unavailable to insurers. The extra premiums are typically very high, but because APKD is rare, the possible cost of adverse selection is low. However, APKD is just one of a significant number of single-gene disorders, and this benign conclusion cannot be assumed to apply to all genetic disorders taken together. Moreover, ignoring known genetic risks in underwriting sets a precedent that could have unintended consequences for the underwriting of nongenetic risks of similar magnitude.     

Optimism and the perceptions of new risks

While many risks, especially new ones, are not objectively quantifiable, individuals still form perceptions of risks using incomplete or unclear evidence about the true nature of those risks. In the case of well known risks, such as smoking, individuals perceive risks to be smaller for themselves than others, exhibiting ‘optimism bias’. Although existing evidence supports optimism bias occurring in the case of risks about which individuals are familiar, evidence does not yet exist to suggest that optimism bias applies for new risks. This paper addresses this question by examining the gap in perceptions of risks individuals have for themselves versus society and the environment, conceptualised as social and/or environmental optimism biases. We draw upon the 2002 UEA‐MORI Risk Survey to examine the existence of optimism bias and its effects on risk perceptions and acceptance regarding five science and technology‐related topics: climate change, mobile phones, radioactive waste, GM food and genetic testing. Our findings provide evidence of social and environmental optimism bias following similar patterns and optimism bias appearing greater for those risks bringing sizeable benefit to individuals (e.g. mobile phone radiation) rather than those more acutely affecting society or the environment (e.g. GM food or climate change). Social optimism bias is found to reduce risk perceptions for risks that have received large amounts of media attention, namely, climate change and GM food. On the other hand, optimism bias appears to increase risk perceptions about genetic testing.     

Cystic fibrosis--a genetic dilemma

Cystic fibrosis is a common genetic disease that usually presents in early childhood as a devastating disease affecting pulmonary function and at times gastrointestinal functioning and nutritional status. Variant forms of this disease have been described, which may have a delayed age of onset or a milder clinical course. Numerous genetic mutations have been described in cystic fibrosis. There are several mutations that are known to be associated with late onset disease or mild clinical disease. Research continues into these genetic mutations and various modifiers that may help to more accurately predict the final phenotypic presentation.     

Healthcare professionals’ perceptions of risk in the context of genetic testing for the prediction of chronic disease: a qualitative metasynthesis

Advances in genomic technologies and a growing trend towards stratified and preventive approaches to medicine mean that increasing numbers of individuals may have access to information about their genetic makeup, and their risk of developing diseases. This is likely to impact on healthcare professionals involved in the delivery of genetic tests, or in supporting patients who are affected by a disease with a genetic risk factor. It is therefore important to understand healthcare professionals’ perceptions about providing these services, and how they feel about communicating information about genetic risk to patients. This paper provides a systematic review and metasynthesis of qualitative research exploring healthcare professionals’ perceptions of genetic risk in the context of predictive genetic testing for chronic disease. Healthcare professionals expressed a range of reservations about the utility of predictive testing in this context. Professionals judged patients’ understanding of risk information to be limited and subject to bias and a range of sociocultural influences. Concerns about the psychosocial impact of genetic risk information were frequently cited, both in relation to individual patients and the wider impact on their families and communities. The need for provision of multidisciplinary support was described. The concept of responsibility was also an important theme. Healthcare professionals recognized the responsibility that accompanies risk knowledge, and that ultimately this responsibility lies with the patient, not the provider. Our analysis suggests that professionals’ evaluation of the utility of predictive genetic testing is influenced not only by resource deficits, but may also be interpreted as a response to challenging ethical and social issues associated with genetic risk, that are not well aligned with current medical practice.     

我国高校青年教师实践能力培育探讨

要培养大学生的实践能力和创新能力,首先教师应该具备较强的实践能力。然而,很多高校教师特别是青年教师实践能力普遍很低,不足以胜任大学生实践能力的培养。因此,文章分析了当前我国高校青年教师实践能力的现状与存在的主要问题,在借鉴国外院校提升教师实践能力成功经验的基础上,重点讨论了如何培育和提升高校青年教师的实践能力。     

Japan Section News

Huge variations in expenditure per life saved have been documented in the USA, Sweden, and Japan. Using an original-position argument, this paper examines normative rationales that might permit departures from equalization of marginal lifesaving investments. The conclusion is that adjustment for identifiability, as reflected in strict benefit-cost analysis, is not justified yet adjustments for consideration of longevity, quality of life and productivity are compelling. It is less clear as to whether factors such as ability to pay, voluntariness and catastrophic potential should influence lifesaving expenditures.     

Newer cardiac imaging techniques: multidetector CT angiography

An update of new developments with multidetector computed tomography (MDCT) coronary angiography is presented. Similar to what has occurred with the introduction of other new technologies such as electron beam computed tomography (EBCT), life insurance medical directors are expected to evaluate a technology before there are sufficient data from large clinical trials. Well-performed studies of the performance of MDCT coronary angiography have only recently appeared. MDCT appears to perform well for excluding significant coronary disease, and will perhaps be useful in emergency room "rule-out" situations. Other applications may be for the diagnosis of significant coronary obstruction (> 75% stenosis), as well as for the evaluation of bypass grafts. Limitations include the requirement for radiologic contrast administration and significant radiation exposure. MDCT does not provide information on atheroma morphology. Given these limitations, MDCT coronary angiography utilization will grow, and it will prove to be a useful tool in specific situations.