Ethical issues of genomics applied to infectious disease

Ethical issues of genomics applied to infectious disease

"Little or no" consideration of ethical issues

While the application to genomics in the context of clinical medicine has received great attention, there are also great strides being made in applying the same tools to infectious disease, according to Jeffrey Kahn, PhD, MPH, Robert Henry Levi and Ryda Hecht Levi professor of bioethics and public policy at Johns Hopkins Berman Institute of Bioethics in Baltimore, MD.

"As the science expands and its results become more meaningful, it is crucial to consider the ethical, legal, and social implications," he says.

Kahn is a co-principle investigator of the GUIDE (Genomic Uses in Infectious Disease & Epidemics) project, along with Gail Geller, ScD, MHS. The team is exploring the ethical, legal, and social implications (ELSI) considerations of applying genomics to infectious disease.

"It is known that genes play a role in the human immune system, and in an individual's response to disease infection, vaccines, and treatment therapies," says Dvoskin.

To date, applications of genomics in public health have focused primarily on chronic diseases such as cancer, heart disease, and diabetes, and behavioral risk factors such as obesity and smoking, notes Rachel Dvoskin, PhD, genetics research analyst and Exploratory Center of Excellence in ELSI Research (CEER) project coordinator at Johns Hopkins Berman Institute of Bioethics.

While there is literature surrounding the ethical and legal issues of infectious disease control, there has been little or no consideration of the public healthrelated ELSI issues that could arise with the application of genomics to infectious diseases and epidemics.

"In this three-year exploratory CEER, we are mapping this novel terrain in preparation for an application to create an institutional center to analyze the ethical, legal, and social issues identified and make policy recommendations for how best to address them," says Dvoskin.

The team is exploring these issues in the context of two case studies of infectious diseases that are transmitted from human to human: hepatitis C (HCV), a chronic, blood-borne disease, and pandemic influenza, an acute, airborne disease.

"In both cases, genetic variation among individuals is known to be associated with response to prevention or treatment of disease or to aspects of infectivity," says Dvoskin. For example, IL-28B genotype is associated with response to HCV antiviral treatment and with the ability to clear HCV naturally. Polymorphisms in the HLA class II molecules are associated with non-responsiveness to influenza vaccine; MBL-2 codon 54 genotype is associated with poor or adverse response to flu vaccine.

"The two disease cases we have chosen will highlight different types of genomics applications and ELSI issues," says Dvoskin. The team foresees ethical challenges emerging around three areas in which genomics is being applied to infectious disease:

• disease prevention, in the context of vaccine safety and efficacy and vaccine distribution and allocation;
• disease infection, involving individual differences in disease severity and transmissibility to others;
• disease treatment, including efficacy of and response to potential therapies, side effects or adverse reactions, and allocation of drug therapies.

Here are some of the potential ethical issues surrounding pandemic flu:

• Identifying sub-populations at increased risk of adverse events may lead to policies not to immunize them, reducing herd immunity for the larger community.
• There is a question as to whether genotyping of health care workers should be mandatory, in order to assign the task of "first response" to those with flu-resistant genotypes.

For HCV, several ethical questions emerge from the discovery that IL28B genotype is predictive of treatment response. One is whether physicians should use different treatment criteria for people with and without the protective gene variant. "Another ethical concern is whether the knowledge that the IL28B variant decreases risk for developing chronic HCV is likely to increase risk-taking behavior," says Dvoskin.

"One size fits all" paradigm

Despite advances in antibiotics and vaccines, death from infectious diseases is the second leading cause of death worldwide, notes Charis Eng, MD, PhD, FACP, chair and director of the Cleveland Clinic's Genomic Medicine Institute in Cleveland, OH.

"Thanks to policies from the most recent Bush administration and the dire straits of U.S. biomedical research funding, there have been no new antibiotics created in the last 10 years," she says.

A major weakness in current infection prevention and control strategies, says Eng, comes from a "one size fits all" paradigm that fails to sufficiently recognize inherent differences in both host and pathogen.

Individuals do not respond equally to identical infectious agents, and pathogens of the same species are more genomically diverse than once thought. "It is incontrovertible that much of this diversity is attributable to genomic variation," says Eng. "Over the past two decades, genomics has provided remarkable insight into susceptibility, resistance, and progression of infection."

Paradoxically, says Eng, the gap between genomics research and public health application remains large.

Using genomics information to precisely delineate antibiotic sensitivity and resistance is already being done across the country. "This is highly effective, but there is no uniform public health mandate," says Eng.

The U. S. Department of Health and Human Services has designated these two public health genomics objectives for Healthy People 2020:

• To systematically identify Lynch syndrome, the most common adult-onset inheritable colon cancer syndrome, and to get patients to proper genetics care;
• To systematically identify heritable breast cancers and to get patients to proper genetics care.

"Both of these are done to a greater or lesser extent in diverse medical centers," says Eng. For example, the Cleveland Clinic Health System has been successful in implementing universal screening for Lynch syndrome.1

Australia has already implemented nationwide screening for Lynch syndrome, and the United Kingdom is about to do so. "This is because it has formally shown value — that patient care is improved, and that this strategy is cost-effective," says Eng.

Efforts to create and maintain centralized databases of genomic fingerprints are needed, urges Eng, to help improve accuracy and efficiency in infectious outbreak detection and rapid effective treatment.

"Ethical issues center around research and the keeping of centralized databases and sample biorepositories regarding identifiability, confidentiality, and ownership," says Eng.

Other ethical issues involve how collected samples might be used in the future, and the extent to which research projects should support the provision of clinical care for research participants.

"Public health infectious disease ethics are slightly behind organ-specific or process-specific genomics, but should seek guidance from these," says Eng.

Reference

1. Heald B, Plesec T, Liu X, et al. Implementation of universal microsatellite instability and immunohistochemistry screening for diagnosing Lynch syndrome in a large academic medical center. J Clin Oncol 2013; 31(10):1336-1340.

SOURCES

1. Rachel Dvoskin, PhD, Genetics Research Analyst/Exploratory Center of Excellence in ELSI Research Project Coordinator, Johns Hopkins Berman Institute of Bioethics, Baltimore, MD. Phone: (410) 614-5594. E-mail: [email protected].
2. Charis Eng, MD, PhD, FACP, Chair and Director, Genomic Medicine Institute, Cleveland, OH. Phone: (216) 444-3440. E-mail: [email protected].
3. Jeffrey Kahn, PhD, MPH, Robert Henry Levi and Ryda Hecht Levi Professor of Bioethics and Public Policy, Johns Hopkins Berman Institute of Bioethics, Baltimore, MD. Phone: (410) 614-5679. E-mail: [email protected].