The concept of vulnerability has long played a central role in discussions of research ethics. In addition to its rhetorical use, vulnerability has become a term of art in U.S. and international research regulations and guidelines, many of which contain specific provisions applicable to research with vulnerable subjects. Yet, despite the frequency with which the term vulnerability is used, little consensus exists on what it actually means in the context of human subject protection or, more importantly, on how a finding of vulnerability should affect the process of research ethics review.

The Common Rule, the centerpiece of the U.S. human subject protection regulations, uses the word vulnerable three times. First, it provides that institutional review boards (IRBs) that regularly review research involving a vulnerable category of subjects should consider including one or more individuals who are knowledgeable about and experienced in working with these subjects.

Vulnerability in research is often understood as a diminished ability to protect one's own interests, manifested by a compromised capacity to give informed or voluntary consent. Certain groups of people are thought to be more vulnerable than others and therefore are at risk of being exploited or mistreated in research. Accordingly, the federal regulations call for additional safeguards to protect vulnerable groups.

There remains some ambiguity and contradiction, however, regarding what groups are vulnerable in research and why,3 since the available codes of research ethics and regulations describe many groups as vulnerable. When so many groups are considered vulnerable, but no specification is offered as to how they are vulnerable or what particular protections are appropriate, the possibility of meaningful safeguards is diminished. In addition, current concepts of vulnerability are usually applied to whole groups of people, without distinguishing between individuals in a group who might truly have a compromised capacity to protect their own interests from those who do not.

Imagine that you possess an indicator for a disease or illness that has nothing to do with your body. It is not a genetic predisposition to acquire cancer or a vice that raises the probability of contracting some dread disease, though estimates of its health risks have placed it on par with having diabetes. It has nothing to do with the environmental pollutants you are exposed to or whether you can afford health care. It is not a physical susceptibility that renders you more easily reachable by the clutches of pathology. No, this indicator of health hinges on certain learned abilities and skills, and it is a barrier to health that is totally within the health field's power and resources to lift.

The condition hinted at above is the inability to speak English proficiently in the United States. Today, more than one-sixth of the United States population speaks a language other than English at home, and this number (approximately 50 million people) is increasing rapidly.

Translational science is a 21st century mission. Government officials and industry leaders are making huge investments in an attempt to transform more basic science discoveries into therapeutic applications. Scientists and policymakers express great excitement about the medical advances that could come with the current bench-to-bedside campaign.

A key step in translational science is the move from animal and other preclinical studies to initial human testing. Researchers ability to predict human effects is limited, and first-in-human (FIH) tests present significant uncertainty. Participants in this form of research face risks and can experience serious, even lethal, harm. Well-known incidents involving Jolee Mohr and Jesse Gelsinger, as well as subjects in the 2006 study of the investigational agent TGN1412, show the dangers that can arise in early human research.

The bench-to-bedside campaign will need many volunteers to participate in early human testing. Investigators and regulators must not allow the policy enthusiasm for translational science to overshadow the commitment to protect human subjects. Participants in exploratory research are diverse and as a group lack characteristics usually associated with vulnerable populations, such as impaired decisional ability or economic or educational disadvantage.

Suppose that someone has a serious illness. The illness will likely lead to significant disabilities, and may even cause death. Existing treatments are unsatisfactory. The patient learns about a clinical trial, in which some allegedly promising new treatment for that illness is being tested.

Such seriously ill patients for whom existing treatments are unsatisfactory have sometimes been categorized as medically vulnerable in the literature. Should these patients indeed be considered vulnerable subjects and be provided with special protections? And if the answer is yes, then what are those special protections? This article explores the possible answers to these questions.

The federal regulations for the protection of research subjects have several provisions addressing the concept of vulnerability. The three subparts Subparts B (pregnant women, fetuses, and neonates), C (prisoners), and D (children) deal with specific categories of vulnerable subjects, but do relatively little to address broader issues relating to vulnerability that might apply to a category such as the medically vulnerable. The Common Rule (Subpart A) is the only section containing general discussions of vulnerability.

The concept of vulnerability has been the topic of considerable discussion in research bioethics, largely because of dissatisfaction with early constructions of the concept that were based on subpopulations of research subjects. These subpopulations have attributes likely to undermine their capacity to provide autonomous informed consent: persons who are relatively or absolutely incapable of protecting their own interests through negotiations for informed consent. Several subpopulations were seen as requiring special protections, including children, pregnant women, prisoners, racial minorities, the economically disadvantaged, the very sick, and the institutionalized. Recent years have witnessed the identification of other subpopulations with attributes that could render them vulnerable, as well. For example, the Council for the International Organization of Medical Societies has named such potentially vulnerable groups as the homeless, nursing home residents, patients with incurable diseases, patients in the emergency department, employees, students, and members of communities who are unfamiliar with modern medicine.

The vulnerability of patients receiving significantly innovative neurosurgical procedures, either as research or as non-standard therapy, presents particularly potent challenges for those attempting to substantially advance clinical Neurosurgical practice in the most ethically and efficacious manner. This beginning formulation has built into it several important notions about research participation, balancing values, and clinical advancement in the context of neurological illness. For the time being, allow vulnerability to act as a placeholder for circumstances or states of being wherein the established checks and balances of power and interest are no longer sufficient in promoting the just treatment of persons. Further, the phrase to substantially advance Neurosurgical practice encompasses radical innovation as well as significant research into new procedures. Finally, few of these explorations involve true randomized placebo controlled trials, but rather they enroll patients rightfully hoping for some benefit by means of undergoing the procedure.

When a neurosurgeon asks me, as an ethicist, to meet with a patient who has medically refractory disease and no good standard therapy options remaining, he is asking for help concerning whether to offer, as a last chance, an unproven therapy as either innovation or research.

Reading Scofield’s scathing indictment of my field, bioethics, reminded me of how it felt, as an American liberal committed to the cause of racial justice, to read Soviet diatribes against American racism published during the Cold War. I shared with the authors a deep commitment to rectify the injustices they protested. Yet, like Scofield, they proffered accounts of events so radically selective and decontextualized that their version of history seemed more akin to fiction than to fact.

Can researchers, interested in novel ways to assess HIV seroprevalence among populations which are otherwise hidden, collect condoms that have been discarded on the ground in a public sex environment (PSE) and test them for HIV? Does the Code of Federal Regulations address this question, and if not, what areas of research ethics might provide guidance to an IRB considering such a study? These questions arose as part of a preliminary study to test the feasibility of collecting discarded condoms from a public sex environment in Massachusetts, and testing contained semen for HIV. Although the methodology of this study is somewhat unusual, the questions raised are not. Researchers, who wish to use other types of abandoned samples such as discarded syringes, hair or saliva samples, or even excess biological samples, commonly confront similar issues, and the analysis utilized here could guide design and review of other studies.

Following the widespread occurrence of birth defects from the use of thalidomide to treat nausea during pregnancy in the 1960s and 1970s, the Food and Drug Administration (FDA) became particularly vigilant about the use of therapeutic agents during pregnancy and in women of childbearing potential. The FDA developed a list that categorizes an agent according to the known (and potential unknown) risks to a fetus. The drug thalidomide falls into Category X: agents that have demonstrated clear risk of fetal abnormalities and whose risks outweigh the benefits of use during pregnancy.

Another Category X drug is isotretinoin, commonly known by its trade name Accutane. Isotretinoin is an oral medication prescribed for severe recalcitrant, nodular acne in patients who are unresponsive to conventional therapy. Isotretinoin has been available since 1982, and it remains the only effective treatment for this condition.

Over the past decades the mortality rate in the United States has decreased and life expectancy has increased. Yet a number of recent studies have drawn Americans attention to the fact that racial and ethnic disparities persist in health care. It is clear that the U.S. health care system is not only flawed for many reasons including basic injustices, but may be the cause of both injury and death for members of racial and ethnic minorities.

In 2002, an Institute of Medicine (IOM) report requested by Congress listed more than 100 studies documenting a wide range of disparities in the United States health care system. This report found that people belonging to racial and ethnic minorities often receive lower quality of health care than do people of European descent, even when their medical insurance coverage and income levels are the same as that of the latter.

The Human Papillomavirus (HPV) vaccine burst onto the market and the legislative scene nearly simultaneously. Marketed as an amazing medical breakthrough, the vaccine GARDASIL prevents infection with four strains of Human Papillomavirus in nave populations; these four strains are responsible for 70% of cervical cancers and 90% of genital warts. Although most agreed that the vaccine was a wonderful medical advancement with the potential to save women's lives, there was strong disagreement about and a vocal public response to legislative attempts to require girls to receive HPV vaccines for school attendance.

The strong public response to HPV vaccine mandates partially stemmed from the sense that this vaccine is different from previously mandated vaccines because it attempts to prevent disease whose sole route of transmission is through sexual contact. Most other diseases covered by mandated vaccines are spread through the air, with little an individual can do in altering their behavior to prevent infection.

In long Midwestern winters, two things are certain: snow and basketball. But two things that you cannot count on are snow day school closures and a home-team collegiate basketball championship. In Kansas last winter, we had both. Winter precipitation was much above average, resulting in a rare invocation of the University's inclement weather policy to cancel classes in early February. And the Kansas Jayhawks basketball team brought home the National Collegiate Athletic Association championship trophy for the first time in two decades. The Chancellor commemorated the achievement with a campuswide celebration, including all-day class cancellation. This is all well and good. I am all for respecting Mother Nature's forces and celebrating remarkable athletic accomplishments.

But the combination of events does leave law professors nearing the end of the semester in a bit of a quandary. How to make up the cancelled classes to ensure compliance with American Bar Association accreditation instructional hours requirements? How to cover the missed course content? How to find mutually agreeable make-up class times and locations with a group of busy, upper-level law students?

As of July 1, 2008, females aged 11-26 years seeking status as permanent residents in the United States must produce documentation that they have received the human papillomavirus (HPV) vaccine before the U.S. Citizenship and Immigration Services will approve their status adjustment. Immigration rights activists and public health officials have objected to this new requirement on the grounds that it is unnecessary and imposes unreasonable barriers to lawful immigration due to its expense. The Supreme Court has generally upheld mandatory vaccination requirements for citizens and non-citizens and has tolerated federal immigration regulations that would be unconstitutional if applied to citizens. However, the HPV vaccination requirement may be arbitrary, unnecessary, and discriminatory as applied to green card applicants who pose no greater threat to public health than citizens who are not subject to the same requirements. Furthermore, the requirement may also impose unreasonable restraints on aliens individual liberties as well as real barriers to immigration.