The Grand Challenges in Global Health (GCGH) initiative is a major effort to achieve scientific breakthroughs against diseases that kill millions of people each year in the world's poorest countries. With 44 projects, more than US$450 million in funding, and scientists from 33 countries, it has the potential to greatly reduce the suffering and death that disproportionately affect the 2 billion poorest people on earth. The 14 Grand Challenges serve seven long-term goals in global health [1], which are shown in Box 1.

Such a significant investment in scientific research must be accompanied by a program addressing the ethical, social, and cultural (ESC) issues that may arise—either in the development and implementation of the research projects themselves, or in the subsequent appropriate use of resultant knowledge and technologies by communities in need (see next paper in this series by Berndtson et al. [2]).

Examples of setbacks as a result of ESC issues involving new technologies or approaches include: (1) the halting of trials of tenofovir (an antiviral medication used to treat HIV) in Cambodia, Cameroon, and Nigeria following claims there was not proper consultation with affected communities [3]; (2) rejection of white anti-malaria bed nets in cultures where that color was culturally sensitive [4]; and (3) Zambia's rejection of genetically modified foods because of perceived health, environmental, and economic risks [5].

The Bill & Melinda Gates Foundation has recognized the need to understand and address ESC issues in the GCGH initiative. In November 2005, the foundation awarded us a grant to develop and run the ESC program for the GCGH. The two goals of the ESC program are (1) to provide an advisory service for GCGH projects on ethical, social, and cultural issues in the short- to mid-term, and (2) to create a research program to facilitate appropriate adoption of the technologies resulting from the GCGH projects in the long-term. Our starting assumptions for the ESC program are that science and technology play a key role in global health and development [6], and that the appropriate development and adoption of technology requires careful attention to the salient ethical, social, and cultural issues.

In this article we describe the ESC program of the GCGH initiative. We emphasize the features of our program that we believe represent valuable innovations in the evolution of ethical and social programs in large-scale science. We also introduce three subsequent articles appearing in this issue of PLoS Medicine that begin to illustrate some of the contributions of the ESC program to date [2,7,8].

What Is Already Known

To our knowledge, the first large-scale science project to address ESC issues systematically was the Ethical, Legal and Social Implications (ELSI) program of the Human Genome Project. In 1988, James Watson determined that 3% of the project's budget should be devoted to ELSI issues, raising this number to 5% in 1991 [9]. Although the ELSI program has stimulated efforts to inform the public about risks in genetic research and to deal with those concerns through research and education projects, a Science commentary on ELSI in 1996 revealed reservations about the program's “blurry mandate” and distance from the applications of the actual science [9]. Watson himself suggested that he saw ELSI initially as a way merely to deflect criticism from those wary of the consequences of genetic research, saying “It kept us from being attacked” [9]. An independent review of the ELSI research programs in 2000 criticized the limited number of voices informing ELSI research and recommended drawing on “theoretical perspectives from outside the traditional community of ELSI researchers” from a “broader array” of disciplines and communities [10].

The Human Genome Project's ELSI program set a standard for addressing ESC issues in large-scale science projects. Subsequent programs such as the International HapMap Project (http://www.hapmap.org/ethicalconcerns.html) and the National Nanotechnology Initiative (http://www.nano.gov/html/society/ELSI.html) have also adopted ESC programs. However, developing world involvement in these initiatives has been limited. For example, HapMap's Populations/ELSI Group, which considers ethical and sampling issues in the HapMap project, links membership to funding. Although China has managed to secure financial support, and therefore membership, Nigeria does not have the financial means to join the group, whose other members include the United States, United Kingdom, Canada, and Japan [11]. All of the participants and contributors attending the 2003 National Nanotechnology Initiative Workshop on societal implications of nanotechnology represented industrialized nations [12].

Our program aims to improve on previous programs by more successfully integrating the ESC activities with the scientific work of the GCGH investigators, and by focusing on ESC obstacles to the successful implementation of effective technologies for and with the developing world.

Preliminary Activities: Advisory Service

The goal of the advisory service is to facilitate the successful and appropriate achievement of milestones in the GCGH projects in the short- and mid-term. Below we discuss the advisory service consultation model and give examples of two advisory service consults.

The ESC advisory service (Figure 1) is designed to address ESC issues identified at the outset of GCGH research projects, as well as challenges encountered as projects progress. At the GCGH kickoff meeting in Seattle in November 2005, we introduced the ESC advisory service to the project staff and to the GCGH program officers. We explained that our goal was not to regulate research or to provide ethical cover. We recognized the expertise and accountability of the investigators and so did not see ourselves as providing a simple guidance function. Rather, our aim was to work in a close, integrated fashion with the investigators on ESC issues arising in their projects and thus contribute directly to the achievement of their milestones.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Figure 1. Consultation Model

The design of the ESC advisory service draws from a consultation model we have successfully used in the past.

https://doi.org/10.1371/journal.pmed.0040265.g001

In the first year of operation, we consulted with 24 of the 44 GCGH projects in varying levels of depth, from the achievement of specific regulatory and oversight milestones to preliminary discussions to scope out approaches to anticipated issues. The remaining 20 projects have indicated no ESC advisory needs at this time, though we will continue to engage the project's researchers to ensure any emerging ESC needs are met. Two in-depth consults (Boxes 2 and 3) illustrate the nature and scope of the advisory service and show responses and/or recommendations, as well as successes and lessons learned.

Based on our experience with the first year of consults, we have implemented a plan to assign an advisory service co-leader (Jerome Singh or James Lavery) and a lead bioethicist (Paulina Tindana or Anant Bhan) to each GCGH project. In this way, ESC team members are developing Grand Challenge–specific expertise. To the extent possible, the assignment of the lead bioethicists reflects their areas of training and expertise. During the initial phase of communication, the co-leader and lead bioethicist define the issues and develop a preliminary strategy for addressing the consult.

In an attempt to stay ahead of emerging issues and consolidate our expertise for anticipated consults, we have also initiated a process of consultation with the GCGH program officers. These relationships with the program officers, who have extensive experience in the GCGH scientific areas, have been instrumental in helping us identify issues arising across Grand Challenges or within individual projects. In addition to occasionally inviting individual program officers to join our bi-weekly advisory service conference calls, we have regular participation of program officers in our bi-weekly full ESC team meetings, as well as occasional face-to-face meetings to discuss specific issues. These close working relationships have allowed us to benefit from the expertise and insights of the program officers in terms of understanding all of the relevant scientific dimensions of the projects, and to better appreciate and anticipate related ESC issues.

We have also developed a database of consults that documents the key issues, work plans, actions, and outcomes of each consult. This database serves as a detailed record of the advisory service activities, and is a key management tool in the evolution and evaluation of the advisory service.

Preliminary Activities: Research Program

The goal of the research program is to fill gaps in knowledge in order to facilitate the successful and appropriate adoption of the technologies resulting from the GCGH projects by communities in need in the long-term. The research program was designed to address cross-cutting issues in the GCGH projects. It has been shaped by a review of the project proposals, the results of the focus groups of GCGH investigators and program staff, and the survey of key informants in the developing world. Perhaps the most significant question addressed by the research program is: Assuming some of the projects are successful and the technologies are developed, how will they reach the communities that need them in the developing world? Below we discuss four aspects of the research program that offer insight into that question.

Next Steps

We believe that the ESC program is an innovative approach to dealing with key ethical issues in a large-scale science program that seeks to improve human well-being in the developing world. Our approach combines conceptual reflection, empirical research, and service activities. It incorporates input from research programs, funders, and the broader community of potential beneficiaries of research. The key features of this program, which may serve as a model for other large-scale science initiatives, are the close linkage of ESC activities to the science projects themselves, and the extensive inclusion of voices from the developing world.

Acknowledgments

The authors would like to acknowledge the contribution of ESC team members in compiling this overview, including Kathryn Berndtson, Emma Cohen, and Dilzayn Panjwani for their help in finalizing this paper. They would also like to acknowledge helpful comments from GCGH program staff, and thank Michael Keating for editorial assistance.