Clinical gene transfer research (GTR) has both a unique history and a complex and layered system of research oversight, featuring a unique review body, the Recombinant DNA Advisory Committee (RAC). This paper briefly describes the process of decision-making about clinical GTR, considers whether the questions, problems, and issues raised in clinical GTR are unique, and concludes by examining whether the RAC's oversight is a useful model that should be reproduced for other similar areas of clinical research.

Clinical GTR is governed by the same oversight system as most clinical trials, with a significant addition: the RAC. Like other research with human subjects, GTR, if it is affiliated with a federally funded institution, must be approved by an institutional review board (IRB) whose activities are governed by the common rule, that is, the federal regulations for protection of human subjects in research. Like other research intended to produce a drug, device, or biologic to be marketed in the United States, GTR is also overseen by the Food and Drug Administration (FDA).

Social epidemiology has made a powerful case that health determined not just by individual-level factors such as our genetic make-up, access to medical services, or lifestyle choices, but also by social conditions, including the economy, law, and culture. Indeed, at the level of populations, evidence suggests that these “structural” factors are the predominant influences on health. Legal scholars in public health, including those in the health and human rights movement, have contended that human rights, laws, and legal practices are powerfully linked to health. Social epidemiology and health-oriented legal scholarship are complementary in their focus and their research needs. Legal scholarship has identified plausible ways in which legal and human rights factors could be influencing health, but empirical evidence has been limited.

Public health ethics, like the field of public health it addresses, traditionally has focused more on practice and particular cases than on theory, with the result that some concepts, methods, and boundaries remain largely undefined. This paper attempts to provide a rough conceptual map of the terrain of public health ethics. We begin by briefly defining public health and identifying general features of the field that are particularly relevant for a discussion of public health ethics.

Public health is primarily concerned with the health of the entire population, rather than the health of individuals. Its features include an emphasis on the promotion of health and the prevention of disease and disability; the collection and use of epidemiological data, population surveillance, and other forms of empirical quantitative assessment; a recognition of the multidimensional nature of the determinants of health; and a focus on the complex interactions of many factors—biological, behavioral, social, and environmental—in developing effective interventions.

It is one of the remarkable and significant consequence of the AIDS epidemic that out of the context of enormous suffering and death there emerged a forceful set of ideas linking the domains of health and human rights. At first, the effort centered on the observation that protecting individuals from discrimination and unwarranted intrusions on liberty were, contrary to previous epidemics, crucial to protecting the public health and interrupting the spread of HIV But in fairly short order, the scope of the health and human rights perspective expanded dramatically to focus on the ways in which the most fundamental social arrangements rendered individuals and communities vulnerable to HIV Racial and ethnic minorities, those who were marginalized, and women were at risk because of their subordinate status. In the face of such an understanding, nothing short of social change could be adequate to the challenge posed by the AIDS epidemic.

In Grimes v. Kennedy Krieger Institute, the Maryland Court of Appeals (Maryland’s highest court) considered whether it is possible for investigators or research entities to have a special relationship with subjects, thereby creating a duty of care that could, if breached, give rise to an action in negligence. The research under review, the Lead Abatement and Repair & Maintenance Study, was conducted from 1993 to 1996 by investigators at the Kennedy Krieger Institute (KKI), an affiliate of Johns Hopkins University.

After briefly discussing the case at the center of this ruling, I consider how ambiguities within the federal research regulations at 45 C.F.R. § 46 contribute to disagreements among reasonable and informed people of good will about what studies should be approved. I argue that Grimes may be understood as placing restrictions on how these regulations may be interpreted and used.

In both academic literature and the media, financial conflicts of interest in human subjects research have come center-stage. The cover of a recent edition of Time magazine features a research subject in a cage with the caption human guinea pigs, signifying perhaps that human research subjects are no more protected from research abuses than are laboratory animals. That magazine issue highlights three well-publicized cases of human subjects research violations that occurred at the University of Oklahoma, the University of Pennsylvania, and Johns Hopkins University.

At St. John Medical Center in Tulsa, Oklahoma, a study that was co-sponsored by the University of Oklahoma Health Sciences Center investigated an experimental vaccine for malignant melanoma. In that case, the chair of the university's institutional review board (IRB) — the committee within each medical institution charged with ethics review of human research projects undertaken at that institution — and the dean of the University's College of Medicine allegedly concealed from both the IRB and the United States Food and Drug Administration (FDA) a report by an outside consulting firm that had found severe deficiencies with the melanoma vaccine study being conducted at the medical center.

Stigma has become an important concept in public health law. It is widely accepted that certain diseases are disfavored in society, leading to discrimination against people identified with them, which in turn has the tendency to drive an epidemic underground—i.e., to make it more difficult for voluntary public health programs to reach and succeed among populations bent on concealing their disease or risk status. The need to reduce stigma and its effects has been used to justify the passage of privacy and antidiscrimination law to protect people with HIV. More recently, stigma has been part of the arsenal of justification for special genetic antidiscrimination and privacy law. Despite its importance, however, there is no single widely accepted definition of stigma in social science, and its relationship to law has been generally under-theorized and unsupported by data, reducing our ability to effectively deploy law and other tools in the anti-stigma cause.

Studies in several developing countries for treatmen to prevent HIV-transmission from mother to child generated considerable controversy in 1997. Critics of the studies argued that basic principles of research ethics were violated. According to the critics, researchers subjected women in developing countries to studies that would have been unethical in the United States (and other developed countries) and that the researchers were therefore engaged in unethical exploitation ofcitizens of the developing countries in which the studies were conducted.

While the critics agreed that unethical exploitation had occurred, they differed on the exact nature of the exploitation. Some observers condemned the researchers for employing a double standard — because the researchers were applying a standard of care that would have been unacceptable in their own country. In the view of these critics, researchers should have been comparing the experimental treatment to established therapy rather than to placebo, as would have been required in the United States or other developed countries.

In the foundational piece in this issue of the journal, “Integrating Law and Social Epidemiology,” Burris, Kawachi, and Sarat present a model for understanding the relationship between law and health. This article uses the case of a specific health condition, the human immunodeficiency virus (HIV) infection, as an opportunity to flesh out this schema and to test how the model “fits” the world of the HIV pandemic. In applying the model to this communicable disease, we hope to illustrate the multitude of ways that laws affect the course of the pandemic as well as the course of an individual’s vulnerability or resilience to the disease, and how the complexities of an individual’s life dealing with the virus interface with the world of laws and legal institutions.

In August 2001, the Maryland Court of Appeals harshly criticized the Kennedy Krieger Institute of Johns Hopkins University for knowingly exposing poor children to lead-based paint. The court’s decision made national news, and is worth examining because it raises several very important issues for research ethics.

The research conducted by the Institute was an attempt to understand how successful different lead abatement programs were in reducing continued lead exposure to children. Previously, Julian Chisolm and Mark Farfel, of John Hopkins University, had disclosed the dangers of traditional dust-generating deleading practices. In the current study, Dr. Farfel and colleagues sought to document the longevity of various lead-based paint abatement strategies.

In April 1999, Dr. Curt Freed of the University of Colorado in Denver and Dr. Stanley Fahn of Columbia Presbyterian Center in New York presented the results of a four-year, $5.7 million government-financed study using tissue from aborted fetuses to treat Parkinson’s disease at a conference of the American Academy of Neurology. The results of the first government-financed, placebo-controlled clinical study using fetal tissue showed that the symptoms of some Parkinson’s patients had been relieved. This research study involved forty subjects, nineteen women and twenty-one men; all suffered from Parkinson’s disease for an average of 13.5 years. In the study, each subject underwent neurosurgery: “four tiny burr holes, drilled through the wrinkle lines above the eyebrows into the skull, to clear a pathway to the brain. But only half received injections of fetal cells into the putamen, the region of the brain that controls movement; the other half received nothing. One year later, three members of the placebo group said their symptoms had improved.” In two-thirds of the transplant recipients, the fetal tissue took hold and seemed to establish a new network to produce the missing neurochemical dopamine.

Over the past decade, the number of clinical trials registered with the Food and Drug Administration (FDA) has increased dramatically. The business of clinical research has become more diverse, involving academic institutions, clinician-researchers in community settings, pharmaceutical companies, and contract research organizations. This growth has been accompanied by increasing concerns about the ethical conduct of research. Much of this concern has been directed to procedural issues including institutional review board (IRB) review, data monitoring, and informed consent forms. However, the protection of human subjects cannot be achieved by relying solely on procedural safeguards. There are more nuanced issues related to recruitment and retention of subjects, and to the process of informed consent, that are generated during the interaction between study staff and subjects. It is only through an examination of these relationships that one can more fully define and understand the challenges of protecting subjects in research.

This article reviews the relationship between managed care and public health. Managed care, with its seemingly infinite structural and organizational variation, dominates the modern American health-care system for the non-elderly U.S. population. Through its emphasis on standarhzed practice norms and performance measurement, coupled with industrial purchasing techniques, prepayment, risk downstreaming, and incentives-based compensation, managed care has the potential to exert considerable influence over the manner in which the health-care system is organized and functions. Given the degree to which the attainment of the basic public health goal of protecting the public against population health threats for which there are known and effective medical interventions depends on the successful interaction between public health policy and the medical care system, the importance of a viable working relationship between public health and managed care is difficult to overstate.

The potential for conflict between public health and medical care is nothing new; indeed, delineating the boundaries of public health to shape and influence medical practice has occupied the energies of policymakers and the medical industry for well over a century.

In public health and the social sciences, there is growing recognition of the role that social context plays in determining health. Frequently, social relations of inequality are among the most important features of social context identified in this work, and emphasis is placed on identifying and addressing these inequalities in order to improve health. Within the field of HIV/AIDS prevention as well, researchers have begun to look beyond individuals for an understanding of the structural causes of HIV-related risk. This research demands that greater attention be paid to the social mechanisms and contextual factors that lead to HIV risk. Among these factors are law and social policy, which form a part of the context in which risk-taking occurs and which can promote both HIV transmission and prevention. On the one hand, laws limiting access to sterile injection equipment have contributed to HIV-related risk behavioxs among injection drug users (IDUS).

As the public profile of bioethics rises, and as litigation about issues ranging from assisted reproduction to gene therapy multiplies, the presence of bioethics experts in a litigation context has become more common. Dozens of appellate opinions refer to bioethics testimony in the lower courts. Today's technical advisory services for attorneys advertise bioethics experts along with experts in scientific fields. A single bioethicist has served as an expert in more than fifty cases. In all likelihood, opportunities for bioethicists to fill the role of testifying expert will grow as medicine and biotechnology become more complex. Bioethics experts have also been involved in several other kinds of litigation-related activities, including investigation, consultation with attorneys, preparing reports that express expert opinions, and explaining and defending these opinions by deposition.

Despite the growth of these activities by bioethicists, they have never been free of controversy, have recently been received with little enthusiasm by the judiciary, and could become highly problematic in the future.

In recent years, consumer debt and the bankruptcy filing rate have received substantial public and media attention in the United States. That attention pales in comparison with widespread concerns and media reporting about health. Yet, both sets of discussions may be relevant to individuals and families facing a combination of health problems and financial problems. In a recent study, nearly half of the sample of individual bankruptcy filers reported they also were dealing with illness, injury, or substantial medical debt.

Whether somethmg other than coincidence explains this correlation is worthy of consideration for those who study health. For some debtors, debt problems may be health-care finance issues; income interruption or financial obligations stemming from health ailments may contribute to financial downfall?

The opposite relationship, however, not only is possible, but potentially more pervasive.

In this issue of the Journal of Law, Medicine & Ethics Peter Clark provides a comprehensive and sound ethical analysis of clinical trials examining the treatment of advanced Parkinson's disease with fetal tissue transplantation. These studies raise profound questions about how clinical trials of surgical interventions ought to be conducted. At stake is not only the ethical basis of such trials, but differing views as to the proper role of science in medicine and its limitations.

Experience with the broader debate on the ethical permissibility of placebo controls has taught us that the choice of control treatment is an aspect of trial design in which ethical and scientific issues overlap. Accordingly, I will highlight, and perhaps expand upon, three issues raised by Clark: What scientific questions ought clinical trials of surgical interventions ask? How should the ethical analysis of risk for such trials be conceived? And, are surgical patients a vulnerable population?

In the fall of 2001, the need for a vigorous and effective public health system became more apparent than it had been for many decades. With the advent of the first widescale bioterrorist attack on the United States, the government's obligation to respond and take steps to protect the public health became self-evident.

Also obvious was the need for of an effective partnership between federal, state, and local officials. Local officials are almost always on the front lines of the struggle against bioterrorism. They are the first to recognize a suspicious case and to provide testing and treatment for the affected population. At the same time, state officials are needed to support and coordinate local efforts, providing an expertise that may be lacking in many communities, especially smaller ones.

But few would doubt that the federal government has a key role to play. The Centers for Disease Control and Prevention (CDC) is expected to lead the epidemiological investigation and provide expertise on how to cope with diseases that remain unfamiliar to most physicians.