Biomedical research is so important that there is a positive moral obligation to pursue it and to participate in itScience is under attack. In Europe, America, and Australasia in particular, scientists are objects of suspicion and are on the defensive.i“Frankenstein science”5–8 is a phrase never far from the lips of those who take exception to some aspect of science or indeed some supposed abuse by scientists. We should not, however, forget the powerful obligation there is to undertake, support, and participate (...) in scientific research, particularly biomedical research, and the powerful moral imperative that underpins these obligations. Now it is more imperative than ever to articulate and explain these obligations and to do so is the subject and the object of this paper.Let me present the question in its starkest form: is there a moral obligation to undertake, support and even to participate in serious scientific research? If there is, does that obligation require not only that beneficial research be undertaken but also that “we”, as individuals and “we” as societies be willing to support and even participate in research where necessary?Thus far the overwhelming answer given to this question has been “no”, and research has almost universally been treated with suspicion and even hostility by the vast majority of all those concerned with the ethics and regulation of research. The so called “precautionary approach”9 sums up this attitude, requiring dangers to be considered more likely and more serious than benefits, and assuming that no sane person would or should participate in research unless they had a pressing personal reason for so doing, or unless they were motivated by a totally impersonal altruism. International agreements and protocols—for example, the Declaration of Helsinki10 and the CIOMS Guidelines11—have been directed principally at …. (shrink)

Do we have the right to deny others access to our body? What if this would harm those who need personal services or body parts from us? Ccile Fabre examines the impact that arguments for distributive justice have on the rights we have over ourselves, and on such contentious issues as organ sales, prostitution, and surrogate motherhood.

: Bioethicists have failed to understand the pervasively paternalistic character of research ethics. Not only is the overall structure of research review and regulation paternalistic in some sense; even the way informed consent is sought may imply paternalism. Paternalism has limits, however. Getting clear on the paternalism of research ethics may mean some kinds of prohibited research should be reassessed.

Should first-in-human trials be designed to maximize the prospect of therapeutic benefit for volunteers, prioritize avoidance of unintended harms, or aim for some happy medium between the two? Perennial controversies surrounding initiation and design of early-phase trials hinge on how this question is resolved. In this paper, we build on the premise that the task of early-phase testing is to optimize various components of a potential therapy so that later, confirmatory trials have the maximal probability of informing drug development and (...) clinical care. We then explore three strategies that investigators might use to manage trial risks while optimizing a therapy, using cell therapy for Amyotrophic Lateral Sclerosis (ALS) as an example. We argue that an iterative application of maximin strategies over successive cohorts and trials, which we call the “risk-escalation model,” establishes a moral principle that should guide decision-making in early-phase trials. (shrink)

The biomedical literature and popular media are full of upbeat reports about the health benefits we can expect from medical innovations using nanotechnology. Some particularly enthusiastic reports portray nanotechnology as one of the innovations that will lead to a significantly extended human life span. Extreme enthusiasts predict that nanotechnology “will ultimately enable us to redesign and rebuild, molecule by molecule, our bodies and brains….”Nanomaterials have special characteristics that could contribute to improved patient care. But the same characteristics that make nanotechnology (...) promising also present risks to humans exposed to nanomaterials. A failure to appreciate these risks could jeopardize the research effort. As others have pointed out, if nanomedical interventions produce unexpected human harm, a loss of public and government support for nanomedicine is likely to follow.Like other forms of medical innovation, novel nanomedical interventions require human testing to evaluate their safety and effectiveness. (shrink)

Novel nanomedical interventions require human testing to evaluate their safety and effectiveness. To establish a proper evidentiary basis for human trials, nanomedical innovations must first be subjected to animal and other laboratory testing. But it is uncertain whether the traditional laboratory approaches to safety evaluation will supply adequate information on nanotechnology risks to humans. This uncertainty, together with other features of nanomedical innovation, heightens the ethical challenges in conducting FIH nanotrials.

The 21st-century translational science campaign could lead to an increase in first-in-human trials. As tests of investigational interventions move from the laboratory to human research, scientists, officials, and review committees should address ongoing concerns about the ethics of FIH trials. In this article, I describe three ethical considerations relevant to all FIH trials: the requirement for adequate preclinical research; study design safeguards; and choice of subject population. I also examine specific ethical considerations relevant to the three subject populations involved in (...) FIH research. I recommend a variety of actions that could increase subject protection and the value of the information generated in FIH trials. (shrink)

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 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. (shrink)

First-in-human clinical trials represent a critical juncture in the translation of laboratory discoveries. However, because they involve the greatest degree of uncertainty at any point in the drug development process, their initiation is beset by a series of nettlesome ethical questions [1]: has clinical promise been sufficiently demonstrated in animals? Should trial access be restricted to patients with refractory disease? Should trials be viewed as therapeutic? Have researchers adequately minimized risks? The resolution of such ethical questions inevitably turns on claims (...) about future events like harms, therapeutic response, and clinical translation. Recurrent failures in clinical translation, like Eli Lilly's Alzheimer candidate semagacestat, highlight the severe limitations of current methods of prediction. In this case, patients in the active arm of the placebo-controlled trial had earlier onset of dementia and elevated rates of skin cancer [2]. Various authoritative accounts of human research ethics state that decision-making about risk and benefit should be careful, systematic, and non-arbitrary [3]–[5]. Yet, these sources provide little guidance about what kinds of evidence stakeholders should use to ensure their estimates of such events ground responsible ethical decisions. In this article, we suggest that investigators, oversight bodies, and sponsors often base their predictions on a flawed and inappropriately narrow preclinical evidence base. (shrink)

Background -- Evaluating the worry -- Proposed justifications -- Human interests and human causes -- Our connection to our contribution -- The value of passive contributions -- Implications -- Objections and the potential for abuse.