What's ELSI got to do with it? Bioethics and the Human Genome Project

Abstract

Two mechanisms for developing public policy in bioethics – an independent commission and the ELSI “un-commission” of the Human Genome Project – are discussed. The author, a private consultant, was staff director of the first US bioethics commission and coordinated the ELSI Program of the US Department of Energy at its outset.

Keywords:

• bioethics
• ELSI
• genetics

Advances in human genetics have raised fears of harmful consequences along with hopes for medical benefits. The downside risks of human genetics (as well as the benefits) are still mostly speculative, but concerns about genetics have been engendered by many worrisome factors, including the genie-out-of-the-bottle example of nuclear physics, the association of genetics with past and potential eugenic practices, and the threat of genetic discrimination. Such concerns have prompted a widespread desire to anticipate, rather than react to, problems that could result from genetic technology. This proactive goal presents policymakers with the difficult challenge of determining, in advance, how genetic technology might be misused and how to prevent such misuse from occurring.

For assistance on complex issues in bioethics, governments have often turned to advisory commissions. In the US, long before the Human Genome Project (HGP) magnified concern about genetics, Senator Walter Mondale proposed that Congress establish a commission to study the ethical, legal, social and political implications of biomedical advances (US Congress 1968). Mondale's proposal was defeated by strong opposition from many prominent physicians and scientists, who testified that they could resolve any issues themselves, without public meddling (Rothman 1991, Jonsen 1998). Mondale persisted, and his proposal was finally incorporated in the law that created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, the first of several advisory commissions that have influenced bioethics policy in the US. In addition to its primary assignment to develop ethical guidelines for human experimentation, Congress directed the National Commission to conduct the study proposed by Senator Mondale (US Congress 1974).

The Mondale study conducted by the National Commission took the form of a Delphi survey of experts. On the basis of this survey, the Commission recommended the creation of a new, specialized advisory commission that would focus solely on the topics of the Mondale study. The National Commission emphasized that the new body should be independent of control by any government agency and comprised of a diverse membership not dominated by the health professions. Such a commission would be able to “anticipate the probable effects of research and technology advances for individuals and society, and … stimulate public participation in decision making” (National Commission for the Protection of Human Subjects 1978).

The National Commission was followed by the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Like its predecessor, the President's Commission was not specifically focused on issues in biotechnology but had a broader mandate that encompassed those issues. The President's Commission, too, recommended the establishment of a body specifically devoted to continuing scrutiny of issues in biotechnology, stressing that such a body should not be dominated by scientists and should be independent of the National Institutes of Health in order to avoid conflict of interest (President's Commission for the Study of Ethical Problems in Medicine 1982).

The next major federal effort in US bioethics was the Ethical, Legal and Social Issues Program (ELSI) of the Human Genome Project (HGP), which began in 1989 and continues to the present. Contrary to the recommendations of the earlier bioethics commissions, the same scientist-administrators who manage the HGP at the National Institutes of Health and the Department of Energy also supervise ELSI. There is no independent body, like a commission, to define the policy issues, determine what research is needed to explore those issues and develop policy recommendations based on the research results. Instead, ELSI is limited to funding extramural research projects in areas that are specified by the HGP's scientist-administrators. The results of the ELSI research are generally published without regard or, indeed, relevance to any policymaking body or procedure. As a result of this restricted focus and methodology, ELSI has produced a large portfolio of academic and professional literature, but little impact on public policymaking. The following discussion explores ELSI's origin, organization and operation that have produced such meager results for policymaking, after a brief review of public policymaking in bioethics.

The moral aspect of bioethics is readily apparent, but the resolution of complex bioethics issues requires a grasp of relevant facts as well as familiarity with principles and other moral guideposts. The facts relevant to an issue in bioethics are often challenging to establish and evaluate, as they may be technical, probabilistic, counterintuitive, disputed, conjectural, private, etc. Moral values may also be difficult to establish and evaluate since they derive – rationally or emotionally – from a variety of sources: social, political, religious, professional, familial, personal, etc. Also, moral values often conflict with each other and are ranked differently by different societies and individuals or groups within a society. Indeed, the complexity of fact-and-value issues arising in medicine and the life sciences gave birth to the field of bioethics four decades ago, in recognition of the fact that these issues required collective analysis reflecting different disciplines and perspectives, including those of patients and human research subjects.

In policymaking settings, the product of bioethics analysis must be pragmatic: a recommendation (or the actual adoption) of the action that is likely to produce the best consequences that reflect the highest values. Pragmatism is not equivalent to utilitarianism; in addition to utility, a pragmatic resolution must be concordant with governing values. There is no formula to reach a correct result in bioethics, no paramount principle to resolve complex issues, only practical problems requiring practical and fair solutions.

The qualifications to do bioethics analysis are straightforward: familiarity with, and ability to analyze, the relevant facts and values. No discipline or profession has a monopoly on these skills or should dominate the process. Of the major disciplines engaged in bioethics, philosophy is useful in raising questions and providing rationale, but the actual resolution of bioethics issues – deciding which course of action to take or recommend – generally relies most heavily on factual analysis and seldom on philosophical insight alone. Law sometimes resolves bioethics issues but in most cases establishes only what is socially permissible, not what is most desirable, or merely imposes procedural requirements rather than a substantive result. The ethics traditions of medicine and science pervade bioethics and provide much guidance, but these professional perspectives have built-in conflicts that practitioners may not recognize when balancing the rights and interests of others. Social science is an obvious source of empirical information about both facts and values, but just as other fields play limited roles in bioethics, social science must be integrated in the broad policymaking process. To be useful in this process, social science must view bioethics policymaking as the goal, not the object, of its study.

To develop bioethics policy, legislatures and government officials have often sought advice from commissions of various sorts, or in the case of human genetics, the decentralized ELSI “uncommission” comprised of academic research projects. A comparison of the first national bioethics commission in the US and the ELSI Program will demonstrate the weakness of the latter mechanism.

Congress established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in 1974 in response to revelations about the Tuskegee Syphilis Study and other human research abuses. The membership of the Commission was broadly representative (five scientists and six non-scientists), and the Commission operated independently, with no oversight by its funding agency. The Commission determined at the outset of its four-year term to “be scientific”, that is, to gather the evidence relevant to the issues in its remit and make policy recommendations on the basis of that evidence.

The evidence gathered by the National Commission concerned the nature of the human research under scrutiny, particularly research with prisoners, children and other populations with reduced capacity to consent. The Commission learned what research was conducted with the particular populations, the goals and accomplishments of the research, and the range of opinion whether the research was appropriate. After the Commission determined what information it needed, staff and consultants conducted the information-gathering activities, including literature reviews, surveys, hearings, opinion papers and site visits. In particular, social scientists assisted the Commission in learning about research in prisons, behavioral research and the performance of Institutional Review Boards.

The Commission reviewed the results of the information-gathering activities, deliberated at length, made findings and recommendations, and explained its rationale. These activities were all conducted in public meetings and reported in the Commission's voluminous publications. Significantly, the law that created the Commission provided for implementation of its recommendations: the Secretary of Health was required to carry out the recommendations or explain why not (US Congress 1974), and in fact most of the Commission's recommendations were implemented in regulations. The credibility of the National Commission was enhanced by its diverse membership, transparency and especially its empirical approach. Finally, the Commission's accomplishment was due to substantial effort by the Commissioners, who met monthly for four years.

In contrast with the National Commission, ELSI has been called an “un-commission” (Juengst 1996) because it consists mainly of extramural research grants with no commission or other independent entity to determine what policy research should be conducted or what to do with the research results. This arrangement has served the needs of its originators, if not its announced purpose. The launch of the HGP in the late 1980s raised concern in Congress that the new genetic knowledge might lead to unfair discrimination and other problems. In an adroit political maneuver that secured public funding of the HGP, the sponsoring government agencies earmarked 3% (soon raised to 5%) of the HGP budget for a research and education program that would examine the ethical, legal and social implications of the HGP, stimulate public discussion of the issues and develop policy options to ensure that genetic information is used beneficially. The ELSI Program would “endeavor to anticipate problems before they arise and develop suggestions that would forestall adverse effects” (Department of Health and Human Services & Department of Energy 1990).

On its face, ELSI reflected an acknowledgement by the HGP's scientific leaders that they were responsible for the societal impact of their work. Diverting funds from a science project to analyze its societal impact and attempting to anticipate social problems that could result from the project were novel steps for both science and government. However, the establishment of ELSI evinced little forethought and a scent of expediency. James Watson, co-discoverer of the structure of DNA and the first NIH director of the HGP, proclaimed ELSI on the spur of the moment at a press conference (Marshall 1996). Although previous recommendations to study the societal implications of biotechnology had contemplated an independent advisory commission, ELSI would simply fund extramural research projects in similar fashion to, and under the same administration as, the HGP's scientific research. There was no apparent consideration whether this science model, which relied on investigator-initiated research under the general direction of the HGP's scientist-administrators, would be useful or appropriate to develop public policy that could potentially question the direction of the HGP's scientific research.

On the other hand, devoting ELSI to academic research grants was an efficient, low-risk mechanism to deflect political challenges to the HGP. The HGP's scientist-administrators established ELSI simply by earmarking funds from their science budget, and they controlled the content of ELSI by determining the boundaries of the funded research. No one would represent the public interest in the administration of ELSI, which would lack at its core an independent, representative entity to analyze the issues, determine research needs, analyze research results and develop well-supported policy recommendations.

The results have not been surprising. To date, ELSI has disbursed over $200 million in grants and continues at a clip of nearly $20 million per year (ELSI Research Planning and Evaluation Group 2000, ELSI Research Advisors 2005). Surely this is the richest bioethics program in history. Despite its size, however, ELSI has not achieved, or even attempted to achieve, the far-reaching results promised by Watson. Instead, the scientist-administrators have focused ELSI inward and downstream, on topics more likely to facilitate and support, than to limit or challenge, the advance of biotechnology.

The general topics selected by the scientist-administrators are: participation of human subjects in genetic research, integration of genetic services in healthcare and protection of genetic information. In addition, ELSI has funded education for genetics professionals and students. Although the broad ambit of “ethical, legal and social implications” of the HGP encompasses these topics, they hardly exhaust the range of social and ethical issues raised by advances in genetics. For example, the use of embryonic stem cells in research has generated a major, worldwide controversy, but not a single grant out of roughly 800 awarded by ELSI deals with this subject. ELSI has also avoided any analysis of the priority accorded genetics in the overall health budget. Nor has ELSI reviewed the role of genetic reductionism in social planning. ELSI has also ignored the implications of genetic research for biological warfare. And regardless of the areas of research designated by the ELSI scientist-administrators, without a policymaking entity to direct and utilize the research, the results are destined to have little impact on public policy.

Essentially, ELSI has functioned as a quality improvement program for genetic research and services. ELSI's narrow focus may be traced to the administrators' interest in promoting genetic science and – the other side of the coin – the lack of an independent mechanism to determine the scope of ELSI and direct the funded research. As designed and managed by the scientist-administrators of the HGP, ELSI lacks scope, independence and a viable mechanism to develop, much less implement, public policy recommendations. One commentator has noted, “It is hardly likely that the [HGP] would have set aside 5 percent of its annual budget for [ELSI] if there had been even the faintest likelihood it would turn into a source of trouble and opposition; and it indeed hasn't” (Callahan 1996).

The publication of academic and professional articles and books generated by ELSI has had little impact on public policy. ELSI researchers have produced information primarily intended for, and communicated to, other academicians and healthcare professionals, not policymakers. Other commentators have noted ELSI's surprising lack of connection to legislative or policymaking activity (Hanna 1995; Jasanoff 2005). This was no accident. Although its stated purpose was to support public policymaking, the virtually unchallenged management of ELSI by scientists inevitably co-opted the program to support of genetic research and services. The irrelevance of ELSI to policymaking is demonstrated by the adoption of legislation protecting genetic privacy and barring genetic discrimination in nearly every state in the US – with little or no input from ELSI. At the urging of Francis Collins, the current director of the HGP at NIH, Congress may soon adopt similar legislation on a national basis. The proponents of this legislation can cite virtually no ELSI research to support their position, but they claim that fear of genetic discrimination is a disincentive to participation in genetic testing or research, even though such discrimination has not actually occurred. Thus, the voluminous research funded by ELSI has had little or no bearing on the policymaking to date in the US regarding genetic discrimination, which instead has been guided by an effort to remove impediments to genetic research and services.

Recently ELSI borrowed a new tactic from US industry: outsourcing. The ELSI outsourcing is not to foreign shores but to so-called “Centers of Excellence in ELSI Research”, that is, academic bioethics programs that already have numerous ELSI researchers. The programs each receive approximately $1 million per year for five years to conduct ELSI research in the following areas: clinical integration of genomics, conduct of human genetic research, conduct of behavioral genetic research and flow of information in genomics research. The first two topics are familiar ones in ELSI; the latter two are new directions for the Program. All four topics fit squarely within the facilitative mission of ELSI – never to challenge genetic science but to enable its advance. This mission is valid as far as it goes, but it is unduly constricted midst the swirl of real and potential genetics-related issues in society.

If Congress allocated a portion of the genome budget to an advisory commission instead of the ELSI Program established by the genome scientists, the effort to develop public policy related to advances in human genetics would depend on such factors as the commission's independence, representativeness, resources, diligence, etc. But it would not be circumscribed from the outset by the genome scientists' self-interest in advancing the HGP.