Explore the Emerging Role of Public Health in Integrating Genomics in Surveillance, Outbreak Investigations, and Control and Prevention of Infectious Diseases
WORKING GROUP DESCRIPTION
According to the 2005 Institute of Medicine workshop report on the implications of genomics for public health, “public health genomics” can be defined as “an emerging field that assesses the impact of genes and their interaction with behavior, diet and the environment on the population’s health.” The priorities for this field are to:
Accumulate data on the relationships between genetic traits and diseases across populations
Use this information to develop strategies to promote health and prevent disease in populations
Target and evaluate population-based interventions
The “public health system,” which includes federal agencies such as the Centers for Disease Control and Prevention, state health departments, and academic public health institutions, is beginning to work closely with basic scientists, professional organizations, consumer groups, and the private sector to “translate” advances in genomics into actions to prevent and control infectious diseases at the population level (Centers for Disease Control and Prevention, n.d.). Increasingly, genetic information from patho-
gens, the human hosts, as well as vectors will be used to understand the pathogenecity, natural history, and genetic susceptibility to infectious agents. These new types of data could have profound influences on how the public health system conducts its surveillance functions, acute outbreak investigations (Lingappa and Lindegren, 2003), and community-level programs for targeting interventions, such as vaccines and medications. A major challenge is how to apply this information on the population level to affect reduction of the burden of infectious diseases in communities. Current public health education has not fully integrated genomics into its basic competences and core curricula. The practicing public health workforce is not adequately prepared to meet the genomics challenge (Institute of Medicine, 2003; Shortell et al., 2004).
What should public health systems do to prepare and respond to the emergence of genomic tools in infectious diseases, in terms of surveillance, outbreak investigations, developing and deploying new interventions (e.g., vaccines), and in its efforts to control of infectious diseases, including bioterrorism events, at the population level?
Consider how public health systems should incorporate genomics into acute public health investigations such as outbreak response. What should be the current priorities? Because host genomic factors are involved in determining who will be sick from infectious agents, should public health systems routinely collect such information in their investigations? Should they develop biologic specimen repositories involving pathology tissues, human DNA, etc., to explore the host response to infectious agents and gene and protein expression profiles?
Consider how public health systems should integrate genomics into surveillance functions for infectious disease occurrence and tracking in the population. While it may be easier to consider pathogen genomics in surveillance, is there a role for routine collection of human genetic information in such data collection? What tools are needed to make epidemiologic surveillance efforts more in real time?
Consider the ethical, legal, and social implications of integrating genomics into public health surveillance and response (e.g., privacy and confidentiality, informed consent) and provide recommendations for action and policy change.
Consider the role of genomics in developing and evaluating community interventions for the control of infectious diseases. Such programs include administration of vaccines and working with communities and providers to implement control and prevention measures. Consider the social factors that also play a role in who gets sick from infectious agents (e.g., poor nutrition because of low socioeconomic status could influence one’s immunity). What should public health systems do to interact with and educate the public and the provider communities in genomics?
Consider the traditional public health data collection categories (e.g., race and ethnicity). Recent articles have underscored one of the consequences of the mapping of the human genome by calling into question our traditional notions of race. Consider how we should categorize individuals given that traditional notions of race and ethnicity are being challenged.
Bamshad, M. 2005. Genetic influences on health: does race matter. Journal of the American Medical Association 294:937-946.
Burris, S., L. O. Gostin, and D. Tress. Public health surveillance of genetic information: ethical and legal responses to social risk (pp. 527-548). Online at www.cdc.gov/genomics/info/books/21stcent5.htm#Chapter27, accessed 2/2/2006.
Centers for Disease Control and Prevention. n.d. Genomics and Disease Prevention website at www.cdc.gov/genomics, accessed 2/2/2006.
Institute of Medicine. 2002. The Future of the Public’s Health in the 21st Century. Washington, D.C.: The National Academies Press.
Institute of Medicine. 2003. Who Will Keep the Public Healthy: Educating Public Health Professionals in the 21st Century. Washington, D.C.: The National Academies Press.
Institute of Medicine. 2005. Implications of Genomics for Public Health: Workshop Summary. Washington, D.C.: The National Academies Press.
Khoury Muin, J., W. Burke, and E. J. Thomson, eds. 2000. Genetics and Public Health in the 21st Century. New York: Oxford University Press.
Khoury Muin, J., W. Burke, and E. J. Thomson. 2000. Genetics and public health: a framework for the integration of human genetics into public health practice (pp. 3-24). Online at www.cdc.gov/genomics/info/books/21stcent1.htm#Chapter1, accessed 2/2/2006.
Lingappa, J., and M. L. Lindegren. 2003. Genomics and acute public health investigations. Genomics and Population Health, United States. Online at www.cdc.gov/genomics/activities/ogdp/2003/chap02.htm, accessed 2/2/2006.
Shortell, S. M., E. M. Weist, M. S. Sow, A. Foster and R. Tahir. 2004. Implementing the Institute of Medicine’s recommended curriculum content in schools of public health: a baseline assessment. American Journal of Public Health 94:1671-1674.
WORKING GROUP SUMMARY – GROUP 1
Summary written by:
Lenette Golding, Graduate Student, Grady College of Journalism and Mass Communication, University of Georgia
Focus group members:
Benjamin Bates, Assistant Professor, Communication Studies, Ohio University
Sally Blower, Professor, Biomathematics, University of California, Los Angeles
Karen Burg, Hunter Chair and Professor, Bioengineering, Clemson University
Robert Cook-Deegan, Director, Center for Genome Ethics, Law and Policy, Institute for Genome Sciences and Policy, Duke University
Lenette Golding, Graduate Student, Grady College of Journalism and Mass Communication, University of Georgia
Isaac Mwase, Associate Professor of Philosophy and Bioethics, National Center for Bioethics in Research and Healthcare, Tuskegee University
Claire Panosian, Professor of Medicine, Division of Infectious Diseases, David Geffen School of Medicine at the University of California, Los Angeles
Mary Reichler, Centers for Disease Control and Prevention
Charles Rotimi, Professor and Director, National Human Genome Center, Howard University
Daniel Salsbury, Managing Editor, Proceedings of the National Academy of Sciences
Todd Thorsen, Assistant Professor, Mechanical Engineering, Massachusetts Institute of Technology
This multidisciplinary group was given the task of exploring the interplay between public health and genomics. Recognizing the wealth of information and opportunities that genomics offers public health, the group discussed ways of bridging the gap between gene discovery and the applica-
tion of genomic tools to surveillance, outbreak investigation, and prevention and control of infectious diseases. These issues were considered broadly, in the context of politics, economics, ethics, race, culture, religion, and the practical limitations of technology and cost.
The first of four working group sessions opened with a discussion about whether recommendations should emphasize tools to detect pathogens or technologies for studying the response of hosts, namely, human beings at risk of catching a disease. Pathogen-centered genomic tools could aid development of rapid diagnostic tests to identify where a pathogen or outbreak originated and whether organisms are drug resistant. Host-oriented genomic tools could be used to assess individual susceptibility to infection and predict response to immunization or specific treatment regimes. Members concurred that genomic tools could broaden scientific understanding of both elements in the host-pathogen equation; they also agreed that neither approach is free of complications.
Lessons from the SARS epidemic
In 2002 an outbreak of a new disease, now called SARS (severe acute respiratory syndrome), began in Hong Kong and was quickly and inadvertently spread by infected people traveling by air. SARS had killed more than 700 people by July 2003. The World Health Organization (WHO) swiftly launched a counterattack against this novel, highly lethal disease. In just seven weeks researchers identified the pathogen and traced it back to its source. In an article that appeared in Reason, a nonpartisan political magazine, in April 2003, Reason’s science correspondent Ronald Bailey wrote, “Thank goodness that SARS broke out in the Genomics Age.” Perhaps if the SARS epidemic had occurred in 1992 instead of 2002, many more would have perished.
The group discussed the SARS epidemic in detail, because it illustrates classic public health issues, such as the fact that prompt identification and containment of any pathogen requires collaboration among government agencies and institutions and cooperation from the general public. In addition, the SARS experience reveals the value of such analytical tools as microarrays and computational genetics. The first step in battling any infectious disease outbreak is identifying the pathogen and its mode of transmission. In the case of SARS, new genomic knowledge enabled scientists to identify the viral culprit with stunning speed. This would not have occurred without WHO’s excellent coordination efforts and collaboration
among the key players in many countries. Driving this effort was public perception—shaped by massive, worldwide media coverage—that SARS was a terrible, lethal, and highly contagious airborne disease that needed to be stopped quickly.
This does not mean that the global public health response to SARS was perfect. A regrettable oversight, according to members of the working group, was the failure to gather information about host genomic factors and susceptibility to SARS from the start of the epidemic. Nonetheless, the group felt that the SARS epidemic of 2002-2003 increased awareness about the importance of good communication, coordination, infrastructure, and surveillance in running effective public health interventions.
Universal issues in the use of genomic technologies: Strategies and solutions
Whether the issue is an infectious disease outbreak or predictive testing for a heritable disease, the group identified five issues that genomic researchers and the public health community must face if genomic tools are to be used effectively. These are:
Educating the public
Identifying racial and ethnic issues in research
Building research capacity
Resolving legal and ethical issues around research
Targeting research to resource-poor versus resource-rich areas
After much discussion, the group decided to concentrate on two of these: public education and coming to terms with racial and ethnic issues in research.
Educating the public: What is the best way to explain the benefits of genomic research to society?
Scientific advances in the laboratory mean little if powerful officials, or a significant percentage of the public, oppose their use; consider how stem cell research has been slowed by public debate and opposition. Although development and use of genomic tools has not dominated the front pages like stem cell research, there is no doubt that some people mistrust biomedical research in general and are especially nervous that information about their own genetic makeup might be misused in various ways, includ-
ing denial of health insurance or employment if it were found out that they had “bad” genes. These attitudes and concerns must be addressed, group members said, for genomics to be used effectively against global infectious disease. Moreover, the group felt that the public needs to be educated as to what a genome actually is.
Public campaigns aimed at building acceptance for genomic analysis of individual DNA samples should promote the social benefits of such research. Most people understand that donating blood in times of crisis is an altruistic gesture of real value to others. The group proposed that genomic research programs—where the results could speed drug or vaccine development, for example—could be marketed as an individual’s opportunity to do something good for society. It is just as important to communicate the social context of such efforts as it is to explain the facts about what genomic tests do and how new genomic tools work.
The media and entertainment industry could play a huge role in supporting, or hindering, genomics. Entertainment education is a strategy that public health systems have used for years. It consists of intentionally placing educational content in entertainment media. Often the media and entertainment industry can be persuasive in terms of behavior in ways that other advocacy methods cannot. The entertainment education strategy has been utilized successfully for numerous public health campaigns, such as HIV/AIDS prevention and for the promotion of national immunization days.
Incorporation of genomics modules into K-12 education, according to state and national science standards, will also be key to instilling long-term awareness and understanding of the relevant issues and developing a knowledgeable public. A campaign to promote acceptance of genomic testing will need to be ongoing as the field grows and advances are made. To be the most effective, genomic campaigns will need to address regional concerns, local health issues, and language differences; in fact, the individuals directing the campaign will first need to be educated about the campaign target regions in order to best serve the local public. “Buy in” from community leaders will be essential.
Racial and ethnic issues in genomic research
Every individual human genome is a history book. If each were read from cover to cover we would discover we are all from the same place; we would discover that we are all Africans beneath our skin. This is true
whether our ancestors later went to Northern Europe and where genes for digesting lactose were selected for, or remained in Africa and developed resistance to malaria parasites. One group member pointed out that group identity is often confused with group ancestry. Instead of being obsessed with relatively minor differences that set apart ethnic groups, the group felt that spreading the message of common origin would help the public understand the importance of global solidarity in the war against disease. But this is a tricky message to convey, because social definitions of race and ethnicity are often confused with genetic origin.
In reality, human genetic makeup is a mosaic, and no gene is unique to one population. Most genetic variation is found in all populations, and occurs among individuals with only a small percentage of variation occurring at the population level. Social and ethnic conceptions of “race” are commonly understood only at the population level. This is why the notion of race is often not necessarily helpful in understanding disease. Some genes that have health effects do, however, occur more commonly in some populations, and correlate roughly with ancestry where such ancestry maps to genetically distinguishable populations. Some health-related factors may, therefore, correlate with “race” or “ethnicity,” although we should understand that the categories are only rough proxies for underlying biological differences. Most “racial” differences are likely to be affected by social, economic, or environmental factors at least as much as genetic differences, but some differences will correlate with genetic differences, and the tools for finding those genetic differences have advanced considerably in the past decade. The important issue here is not race itself but the genes that predispose a person to disease.
The group reflected on BiDil, an antihypertensive drug to treat congestive heart failure that the Food and Drug Administration (FDA) recently approved specifically for use in self-identified African-American patients. This is the first drug approved for use on a racial basis, and the FDA took this step after this medication failed to show efficacy in a large, mixedrace sample but performed significantly better in a smaller follow-up trial restricted to a self-identified group of African Americans. No genomic data were collected in the trials; instead, race—a much cruder and self-selected “identifier”—was used as the inclusion criterion for the follow-up trials.
As a consequence, the group agreed that it is impossible to determine whether race, ethnicity, or environmental factors explain why BiDil appears to work better in some people than others. More to the point, if the
underlying differences are biological, attributable to gene frequency differences, then only some African populations (and hence African Americans) would have the high-frequency alleles and others would not. It is extremely unlikely, for example, that those from sub-Saharan Africa and those from northwestern Africa and those from northeastern Africa would all have the same allele frequencies, given the high level of diversity within Africa. It is also highly likely that some non-African populations also have varying allele frequencies, and so some individuals within those populations could benefit. By using a social measure, such as self-identified race, without the underlying data about genetic variations, the story cannot be understood, and clinical decisions are based on a rough heuristic. This is unfortunate when we have in hand the technologies to do the genomic analysis that could sort out the causal pathway. Overall, the group felt the BiDil study represented a missed opportunity to correlate genomic information with drug efficacy.
The story of race and BiDil is a cautionary tale for host differences in response to pathogens. There are apt to be population differences, particularly for pathogens that have co-adapted in particular regions over long periods of time, so there has been selection pressure on both pathogens and human hosts that may well map to geographic areas and environmental factors that influence the prevalence of specific infectious diseases. It would be sad, indeed, if the story stopped at “race” when in fact, the underlying story is specific environmental factors, host factors, or pathogen differences that could be illuminated by genomic tools.
Benefits to society
The group felt strongly that if the wealth of information stored in human genomes is going to be harvested for the good of humankind, then social, political, and economic barriers and global collaborations must be addressed. The intersection of patients, government, politics, and genomics is often a cacophonous and confusing place. The full potential of the genomic revolution will not be easily realized. The exchange of genomic information across international borders involves delicate political negotiations as well as vast expenditures of capital, while guaranteeing individual rights and ensuring that data will be used for good, not evil, purposes. The exchange of genomic information will require leadership and will mandate education of the leadership such that local traditions and customs are re-
spected and local “buy in” is ensured. These challenges are well worth tackling, however. Stepping back to look at the big picture, the group emphasized that the true promise of genomic technology is saving lives and preventing human misery in all the nations of the world.
WORKING GROUP SUMMARY – GROUP 2
Summary written by:
Corey Binns, Graduate Student, Science Journalism, New York University
Focus group members:
Corey Binns, Graduate Student, Science Journalism, New York University
Ronald W. Davis, Professor of Biochemistry and Genetics and Director, Stanford Genome Technology Center, Stanford University School of Medicine
Georgia M. Dunston, Professor, Microbiology, National Human Genome Center, Howard University
Stephanie Malia Fullerton, Assistant Professor of Medical History and Ethics, University of Washington School of Medicine
Lyla M. Hernandez, Senior Program Officer, Board on Health Sciences Policy, Institute of Medicine
Ezra C. Holston, Assistant Professor, School of Nursing, University of California, Los Angeles
Barbara R. Jasny, Supervisory Senior Editor, Science
Rima F. Khabbaz, Acting Deputy Director, National Center for Infectious Diseases
Hod Lipson, Assistant Professor, Mechanical and Aerospace Engineering, Cornell University
Daniel Oerther, Associate Professor, Civil and Environmental Engineering, University of Cincinnati
Anne W. Rimoin, Assistant Professor of Epidemiology, University of California, Los Angeles, School of Public Health
Marc S. Williams, Director, Clinical Genetics Institute, Intermountain Healthcare
Back in 1918 it could take weeks to travel from one country to another, and yet the Spanish flu pandemic claimed more than 20 million lives as it spread around the globe. Today one can travel halfway around the world in a matter of hours and disease can spread farther and faster than ever before. Fast-paced international travel and trade have brought the world closer together. This new intimacy has brought infectious disease to the forefront of global public health issues. Thus, infectious disease control is now a shared burden—as a growing threat in developed nations, and a clear and present danger in developing nations—and it is therefore a perfect place for a new science like genomics to play an important role. The need to develop new approaches to fight infectious disease was evident in the sentiments of scientists, engineers, and medical researchers gathered in Irvine, California, at the Third Annual National Academies Keck Futures Initiative Conference.
Although the developed world focuses much of its medical research on the diagnosis and treatment of chronic diseases, the developing world is constantly compromised by infectious disease. In these countries, people still suffer from a lack of basic care, such as unclean drinking water, malnutrition, and poor sanitation.
Genomics is a discovery science whose specific applications have yet to be completely realized. While it is difficult to predict exactly how much benefit will result from investing in this kind of research, the time is ripe for public health to begin to explore its potential contribution to mitigating illness and death from infectious diseases. Thanks to the Human Genome Project and enthusiastic news coverage, genomics has received a lot of public attention. But celebrity can result in mistaking genomics for the answer to just about everything in health care, and proponents risk overselling its potential. Aware of these dangers, the 12 members of the group discussed the future of genomics in the battle against infectious disease.
The group agreed that it is essential to set priorities with respect to how best to proceed in applying innovative science in the fight against infectious disease. While innovative science is essential to advance the knowledge base for public health, resource limitation is an omnipresent barrier to improving public health. The investment in genomic science has to be balanced against opportunities for implementation of programs that use inexpensive intervention. For example, a simple bed net to protect against malaria-infected mosquitoes may be just as effective, and far cheaper,
than high-tech treatments based in genomic science. Investment in genomic solutions must therefore be viewed through the long-term lens of the opportunity cost—that is, what will we not be able to afford to do if we spend resources on genomics, and what benefits are likely to accrue in the future.
To help understand the etiology and pathogenesis of a disease, determining the genetic sequence of a pathogen might be a higher priority than sequencing the human hosts, because sequencing the human genome costs are enormous and may yield less information about the infectious disease. While resistance and susceptibility factors in the human genome will no doubt prove important in the future, the price of such discovery has to be balanced against more pressing public health needs. In addition, diseases carrying the highest burdens should be given the highest priority for such research, so that the public benefit to scientific discoveries is possible. Time and resources should be allotted appropriately so that these diseases, namely AIDS, malaria, and tuberculosis, are studied first. Resources should also be given to apply genomics to further research and development of new vaccines and medications because vaccines have historically topped the list of groundbreaking improvements made to public health. Finally, a focus should also be placed on identifying and characterizing specific disease-causing organisms in order to break the chain of disease transmission. If genomics can facilitate this activity, then the expenditure of resources will be justified.
It is clear that genomics fits into the circle of public health. It is important, and not too early, to invest in genomics research—a balanced public health portfolio should include allocating and utilizing resources in discovery science. Analysis of large and diverse kinds of data will be crucial. For instance, host genomic research may lead to a better understanding of susceptibility to infections and risk for disease, as well as the beneficial and adverse effects of drugs and vaccines. The group supported the idea of a bioresource—a place where quality-controlled information could be collected, analyzed, and applied to diagnose, treat, and prevent disease.
Determining exactly what goes into the bioresource was one of the first matters to tackle. In addition to information that is traditionally collected (such as epidemiologic and demographic data), biosamples, ecological information, and genotypic information on pathogens and hosts should also be compiled. The locations of collection and storage sites must be geographically distributed to ensure that participating countries and organizations are engaged and share ownership and responsibility in maintaining the bioresource—a model of data and information gathering that contrasts
with the more “colonial” model of data reposing only in the first world. Designers of the bioresource must place a strong emphasis on standardizing the information collected and enforcing quality control. This will ensure that researchers and healthcare professionals who use the bioresource for diagnoses are working with accurate, standardized datasets.
The group also agreed that the data that come out of the bioresource are as important as the resources devoted to it. Therefore, the resource must be managed as an intelligent system that learns and adapts, continually improving its ability to predict and diagnose health problems as more information is collected in the system. As the study of genomics matures and more discoveries are made, the bioresource would be built to continually adjust to these new insights with new applications. Finally, and key to its success, the bioresource’s output of information has to be almost universally accessible: easy to use by anyone from anywhere.
The benefits of such a bioresource could be far-reaching, not only as a research tool but also as a device to improve public health. Programs for collecting samples and information for single diseases exist: preexisting HIV and malaria projects act as good starting points from which to develop a larger resource that covers multiple diseases. An excellent model is the Global AIDS Program, which partners with communities, scientists, and public officials to prioritize health concerns and direct prevention programs appropriately. However, the Global AIDS Program funding is specifically allocated for prevention programs, and not for research, which would be a crucial additional benefit of the proposed bioresource.
At the same time, it is important to remember that genomics can be successful only if the scientific community takes the time and energy to teach the public how it will improve their health, because of the inherent need for collaboration between the two groups. The group unanimously agreed that education, in the form of a dialog among all parties, is essential to promoting the use of genomics as a public health tool, especially when scientists need the cooperation and understanding of the public to collect genetic information in the form of blood or saliva samples. The public can in turn teach the scientific community what health issues are of greatest concern to them and offer insight into environmental and social aspects of pathogenicity. Both sides have something to learn from each other, and the process will help everyone build trust in the science and one another.
The public’s fears that new technologies may be misused or create inequalities can be put at ease only by taking seriously, and then frankly addressing, their concerns. The public may be opposed to a bioresource
because of its potential to be used inappropriately and possible negative implications from collecting genetic information from infected individuals. Discrimination has historically been a complication of communicable disease outbreaks. Characterization of lepers as unclean is but one example of the stigmatization resulting from infectious disease. Genetic identification gives the public cause to worry about another form of discrimination. We hope that by educating both healthcare workers and the public, we can prevent these problems.
The task of winning over the global public is never easy. With the social and economic disparities that already exist between the developing and the developed nations, it is difficult to make public health programs attractive to those who are uncertain of their place in the definition of “public” health. The bioresource could potentially serve as a tool to help engage all participating and interested parties in the collection, storage, analysis, and dissemination of the information. However, it will likely be a challenge to articulate the message so as to compel a strong commitment to investing in this as a shared public health global resource.
The International Human Genome and HapMap project exemplify the inherent challenges of equality in such ambitious global health initiatives. The principle behind the project is to make all information freely available to any scientist in the world. While this open access model appears wholly equitable, many scientists and the public can’t use the open access model for human genome sequence and HapMap data because they have neither the training, equipment, nor the funding to make use of the available information. Without a commitment to provide public education and open access to equipment, resources such as the human genome sequence and HapMap (or the proposed bioresource) will have only limited impact, particularly for disenfranchised groups and those in traditionally underserved communities.
In addition to solving the problems of inequality and global accessibility of the resource’s assets, there are many ethical concerns that come with a system as encompassing as the group’s proposed bioresource. When donating genomic material to a biobank like the bioresource, participants are typically expected to provide consent for the use of such materials in subsequent research. In exchange, investigators pledge to protect confidentiality and assure contributors that their genetic information will remain secure. Safety is of utmost importance with any repository of infectious materials, and steps must be taken to protect the resource from any harmful misuse of its samples. However, individuals will also have compelling interests in
knowing the health status of themselves and their families, especially in the cases of treatable diseases.
With genomics still in its infancy, now is the perfect time to concentrate on the challenges and promises of this new science in winning the battle against common infectious diseases in their threat to human life and the public health.