Genomics and infectious disease: a call to identify the ethical, legal and social implications for public health and clinical practice

Gail Geller¹²³⁴^*, Rachel Dvoskin¹, Chloe L Thio², Priya Duggal⁵, Michelle H Lewis¹,Theodore C Bailey¹², Andrea Sutherland⁶, Daniel A Salmon³⁶ and Jeffrey P Kahn¹⁴

*Corresponding author: Gail Geller ggeller@jhu.edu

Author Affiliations

¹Berman Institute of Bioethics, Johns Hopkins University, Baltimore 21205, MD, USA

²Department of Medicine, Johns Hopkins University School of Medicine, Baltimore 21205, MD, USA

³Department of Health, Behavior & Society, Johns Hopkins University Bloomberg School of Public Health, Baltimore 21205, MD, USA

⁴Department of Health Policy and Management, Johns Hopkins University Bloomberg School of Public Health, Baltimore 21205, MD, USA

⁵Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore 21205, MD, USA

⁶Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore 21205, MD, USA

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Genome Medicine 2014, 6:106 doi:10.1186/s13073-014-0106-2

The electronic version of this article is the complete one and can be found online at:http://genomemedicine.com/content/6/11/106

Published:

18 November 2014

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Abstract

Advances in genomics are contributing to the development of more effective, personalized approaches to the prevention and treatment of infectious diseases. Genetic sequencing technologies are furthering our understanding of how human and pathogen genomic factors - and their interactions - contribute to individual differences in immunologic responses to vaccines, infections and drug therapies. Such understanding will influence future policies and procedures for infectious disease management. With the potential for tailored interventions for particular individuals, populations or subpopulations, ethical, legal and social implications (ELSIs) may arise for public health and clinical practice. Potential considerations include balancing health-related benefits and harms between individuals and the larger community, minimizing threats to individual privacy and autonomy, and ensuring just distribution of scarce resources. In this Opinion, we consider the potential application of pathogen and host genomic information to particular viral infections that have large-scale public health consequences but differ in ELSI-relevant characteristics such as ease of transmission, chronicity, severity, preventability and treatability. We argue for the importance of anticipating these ELSI issues in advance of new scientific discoveries, and call for the development of strategies for identifying and exploring ethical questions that should be considered as clinical, public health and policy decisions are made.

Introduction

Genomic information offers the opportunity for more personalized treatment and prevention [1] in clinical practice and public health settings. Until recently, such efforts have focused largely on common, complex diseases (for example, cancers, heart disease, neurodegenerative diseases) and less common inherited diseases; examples of such efforts include risk screening, diagnostic sequencing and pharmacogenomics. Now there is growing interest in the application of genomics to the management of infectious diseases and epidemics [2], which are among the top global public health burdens [3]. Rapid and large-scale sequencing of pathogen genomes, which provides stronger and more accurate evidence than was previously possible for source and contact tracing, is being applied widely for disease outbreak management [4] - most recently and publicly in the case of the Ebola outbreak in West Africa [5],[6]. Additional uses include precise diagnosis of microbial infection, describing transmission patterns, understanding the genomics of emerging drug resistance and identifying targets for new therapeutics and vaccines. There is growing evidence that, as well as pathogen genetic factors, host genetic factors and the interaction between host, vector and pathogen influence variability in infection rates, immune responses [7],[8], susceptibility to infection, disease progression and severity, and response to preventive or therapeutic interventions [9],[10]. As such, genomic research is improving our understanding of infectious disease pathogenesis and immune response and may help guide future vaccine development and treatment strategies [11]–[18].

While the past few years have seen substantial federal and private research funding for infectious disease genomics research, there has been little discussion of the possible ELSIs - for individuals, groups or larger society - of using genomic information in the management of infectious disease. This gap may be explained in part by the current paucity of scientific advances in genomics that have practical applications to infectious disease management. Although it may be premature, we must nevertheless anticipate the possibility of ELSI-associated challenges in the future. This Opinion aims to anticipate what some of these issues might be and under what conditions they could arise. We argue that these considerations - even as the science is still developing - should become part of the agenda of researchers, clinicians, policymakers and public health officials so that the benefits of genomic applications to infectious disease are maximized while potential harms to individuals and populations are minimized.

We begin by acknowledging the existing scholarship on ELSI issues in the genomics of non-communicable diseases, and the ethical and legal issues surrounding infectious disease management. Then we briefly describe some of the epidemiologic characteristics and recent genomic advances associated with four particular infectious diseases - Ebola, pandemic influenza, hepatitis B and tuberculosis - that have large-scale public health consequences but differ in terms of ease of transmission, chronicity, severity, preventability and treatability, factors which affect a range of ELSI issues. In this section we also consider the situations under which the use of genomic information might or might not be appropriate in the management of infectious diseases. Finally, we describe some of the major ethical, legal and social issues that arise in the context of genomics and how they may play out in the management of these four specific infectious diseases.

Relevant ethics scholarship: what we know and what might be ahead?

More than two decades of ELSI research on the application of genomics to complex diseases has produced many insights that are also relevant to infectious diseases [19]. With regard to genetic susceptibility testing in a clinical setting, issues include the reliability, validity, confidentiality and disclosure of genetic information. In the case of clinical next-generation sequencing, and in genetic cohort studies and biobanks, pertinent issues include the interpretation of data, data storage, data sharing, informed consent and identifiability/privacy [20]–[26].

However, a number of factors are unique to infectious disease, highlighting the importance of investigating whether novel ELSI issues or variations on existing issues might emerge from the application of genomics in this context. Importantly, the nature of disease transmission differs from that in other types of disease, which has implications for who is at increased risk. Inherited forms of non-infectious diseases exhibit vertical transmission - from one generation to the next. By contrast, infectious diseases can be transmitted horizontally (in addition to vertically) to unrelated or unknown individuals, and those at risk of exposure are often unaware of their risk. In addition, in the case of infectious diseases, potential benefits or harms of healthcare policy accrue to the entire population - as in the case of vaccination - in keeping with the goals of public health. The ethical tensions between the goals and implementation of personalized medicine and those of public health, though not new, are highlighted by the application of genomics to infectious disease management.

Existing literature on infectious disease policy, ethics, and law, outside the context of genomics, describes the potential for stigmatization of individuals or subpopulations, the challenge of balancing individual interests and protections (for example, privacy, autonomy, freedom of movement) against risks of harm to others and to public health, issues of justice, and employer or health professional obligations [27],[28].

At the intersection of genomics and infectious diseases, there has been some discussion of the ELSIs of using pathogen genomics for source and contact tracing [29]–[31], but little attention has been paid to the ELSI issues regarding testing for and using host genetic information in infectious disease prevention and control. As shown in Figure 1, the introduction of genomic information to infectious disease management may complicate or exacerbate existing ELSI issues, or create variations on existing challenges for clinical practice, public health and policy making.

Figure 1. Status of ELSI issues at the intersection of genomics and infectious diseases. In the near term, the ELSI issues that arise at the intersection of genomics and infectious disease are likely to reflect new twists on existing ELSI challenges. In the future, as new scientific discoveries elucidate important host-vector-pathogen interactions, novel ELSI issues might emerge; implications for individuals and society are as yet unknown and unpredictable.

Infectious diseases: epidemiology, characteristics and recent genomic advances

Infectious diseases account for a significant component of disease burden worldwide, and are responsible for a large proportion of morbidity and mortality across all areas of society [3]. Infectious diseases vary by mode of transmission (human to human, vector-borne, waterborne, and so on) and type of pathogen (for example, bacterial, viral) [2]. Infectious agents can cause acute illness (for instance, influenza) or chronic illness (such as with hepatitis B virus (HBV) and HIV), and chronic illnesses can sometimes occur with few or no symptoms until the disease has become significantly advanced.

Strategies for the clinical management and public health control of different infectious diseases vary depending on the acuteness and chronicity of infection, infectivity and virulence of the causative pathogen, modes and ease of transmission, and whether there are effective treatments, vaccines, or other means of prevention. These factors, alone or in combination, are important determinants of the ELSI issues that may arise with genomic applications to infectious disease. For example, whether a disease is transmitted among humans through casual or close contact influences who is at increased risk and whether they are aware of their risk. Or whether a highly contagious disease is preventable or treatable may influence the decision to implement liberty-limiting policies. The genomic variants associated with infectious diseases may be viewed as another characteristic that may or may not be useful in infectious disease management.