Mark Greene

Safety issues in cell-based intervention trials

We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects of stem cell biology pose unique challenges. First, tension regarding the use of human embryos may complicate the scientific development of safe and effective cell lines. Second, because human stem cells were not developed in the laboratory until 1998, few safety questions relating to human applications have been addressed in animal research. Third, preclinical and clinical testing of biologic agents, particularly those as inherently complex as mammalian cells, present formidable challenges, such as the need to develop suitable standardized assays and the difficulty of selecting appropriate patient populations for early phase trials. We recommend that scientists, policy makers, and the public discuss these issues responsibly, and further, that a national advisory committee to oversee human trials of cell therapies be established.

Public Stem Cell Banks: Considerations of Justice in Stem Cell Research and Therapy

If stem cells fulfill their therapeutic promise, moving them from the laboratory into the clinic will raise several concerns about justice. One concern is that, for biological reasons alone, stem cell-based therapies might not be available for every patient who needs one. Worse, depending on how we address the problem of biological access, they might benefit primarily white Americans. We can avoid this outcome—although at a cost—by carefully selecting the stem cells we make available.

To Restore Faith and Trust: Justice and Biological Access to Cellular Therapies

Stem cell therapies should be available to people of all ethnicities. However, most cells used in the clinic will probably come from lines of cells stored in stem cell banks, which may end up benefiting the majority group most. The solution is to seek additional funding, earmarked for lines that will benefit minorities and offered as a public expression of apology for past discrimination.

New Dog: Old Tricks

With the birth, on December 22, 2001, of CC, the first kitten cloned from the cells of an adult cat, Genetic Savings & Clone (GSC) reached a very newsworthy milestone in its progress toward commercial cloning of companion animals. When biotechnology meets the headlines, the story holds both scientific and ethical fascination. Recognizing the ethical dimension of its work, GSC has established a code of ethical practice (outlined by Hawthorne, 2002/this issue) to which all its employees are contractually bound. In this article I will examine the strategy underlying that code of ethics. Hawthorne (2002/this issue) describes an overwhelming response to news of GSC’s project, a response that clearly indicates the enthusiasm with which many people would greet the opportunity to clone a beloved companion. Cloning may offer companion animal caregivers (pet owners) a way to increase their chances of securing a new dog or cat with physical and behavioral qualities similar to those of a much-loved companion of many years. However, cloning is not a technology of reincarnation. Cloning does not buy immortality; it is not cheating death. Cloning is no more a way to extend the life of an individual animal than having a genetically identical twin is a way for one individual to live two lives simultaneously—twins are distinct individuals, and so are clones. Even so, the desire to find a close match for an old animal friend is easy to understand. It also is easy to understand the opposite feeling. Many devoted cat and dog owners express vehement opposition to the idea of replacing their current companion with a clone. However, there is no ethically legitimate move from “I don’t want X,” directly to “X is wrong and others should be denied access to X.” GSC need not defend itself against simple preferences, regardless of the evangelical passion with which such preferences are held. The burden is on objectors to JOURNAL OF APPLIED ANIMAL WELFARE SCIENCE, 5(3), 239–242 Copyright

Consenting to uncertainty: challenges for informed consent to disease screening--a case study.

This paper uses chronic beryllium disease as a case study to explore some of the challenges for decision-making and some of the problems for obtaining meaningful informed consent when the interpretation of screening results is complicated by their probabilistic nature and is clouded by empirical uncertainty. Although avoidance of further beryllium exposure might seem prudent for any individual whose test results suggest heightened disease risk, we will argue that such a clinical precautionary approach is likely to be a mistake. Instead, advice on the interpretation of screening results must focus not on risk per se, but on avoidable risk, and must be carefully tailored to the individual. These points are of importance for individual decision-making, for informed consent, and for occupational health.

The Indeterminacy of Loss

Cystic Pete vs. Dr. Moreau : April 25, 2053 Cystic Pete was conceived, in vitro, at Dr. Moreau’s fertility clinic. Routine genetic testing, prior to fertilization, revealed that both the egg and the sperm carried a recessive cystic fibrosis gene. However, Dr. Moreau did not carry out standard genetic repair of the gametes, and Pete now suffers from cystic fibrosis. Pete seeks compensatory damages. Moreau does not deny his negligence. Instead, he argues that Pete has not been harmed. For Pete to have been harmed, it must be that Pete himself would have been better off had the repair been carried out. However, genetic intervention would have resulted in a person with a genome significantly different from Pete’s actual genome. According to Moreau, any such person would not have been Cystic Pete. Thus, Cystic Pete would not have been better off had the genetic repair been carried out. Rather, he would simply not exist and a different person, one without cystic fibrosis, would have developed in his stead. Moreau’s defense is that, because Pete enjoys a worthwhile existence and he owes that existence to the absence of genetic intervention, Cystic Pete has not been harmed and is therefore not owed compensation.

Saving a life but losing the patient

Gregor Samsa awakes to find himself transformed into a gigantic bug. The creature’s inchoate flailing leads Gregor’s sister to conclude that Gregor is no more, having been replaced by a brute beast lacking any vestige of human understanding. Sadly, real cases of brain injury and disease can lead to psychological metamorphoses so profound that we cannot easily think that the survivor is the person we knew. I argue that there can be cases in which statements like, “It’s just not Gregor anymore,” are not merely figures of speech. With this in mind, I consider three possible results of saving a biological life: (1) ordinary cases where saving the life will save the person, with strong duties to save the life; (2) cases where the intervention needed to save the life will replace the person, with strong duties not to save the life; (3) cases in which it is indeterminate whether the person will be saved or replaced. How should we think about indeterminate cases? Impersonal ethical considerations miss the point, while standard person-affecting considerations are inapplicable. I suggest turning attention away from survival towards a richer focus on what I call “personal concern.” I show how considerations of personal concern, unlike those of self-interest, need not be tied to survival and how this allows personal concern to provide a basis for ethically substantive discussion of cases where saving a life might result in losing the patient.

Roberts on Depletion: How Much Better Can We Do for Future People?

Suppose that Depletion will reduce the well-being of future people. Many of us would like to say that Depletion is wrong because of the harm to future people. However, it can easily be made to seem that Depletion is actually harmless – this is the non-identity problem. I discuss a particularly ingenious attempt by Melinda Roberts to attribute a harm to Depletion. I will argue that the magnitude of Robertss harm is off target by many orders of magnitude: it is just too tiny to explain the intuitive wrong of Depletion.

A Project to Clone Companion Animals

Mostly I agree with Greene’s (2002/this issue) thoughtful analysis of our ethical policies. Greene brands us at Genetic Savings & Clone (GSC) “consequentialists”—one of the nicer labels we’ve been asked to wear. Although we at GSC are mindful of the consequences of our actions, it is not true that we have “nothing to say to critics who charge that satisfying the fancy of a few wealthy dog and cat owners does not justify cloning as a means” (Greene, 2002/this issue, p. 238). One could make the same claim about all nonessential products—that is, most products. Can anyone seriously argue that Porsche’s new sports utility vehicle is really justified when millions are still starving? In a capitalist economy, consumer demand and the ability to fill it are all the justifications you need. At Genetic Savings and Clone, we also focus on potential harms to surrogates and clones because, unlike issues of justification and self-indulgence, the suffering of sentient beings is inarguably significant. To the extent the harms are not zero, one also must consider potential benefits—which, I suppose, simply restates our consequentialist creed. Greene (2002/this issue) criticizes GSC’s Code of Bioethics for lacking any method of monitoring the promised outcomes. He misses the essence of the Code, a set of public commitments made under the glaring lights of public scrutiny. As long as GSC’s work is controversial, we will remain subject to scrutiny. The fulfillment of GSC’s commitments will be easily verified. Bok’s (2002/this issue) critique of GSC’s work is more severe than Greene’s (2002/this issue), right up to her blunt conclusion: “People who want to clone their pets must be either mistaken about what cloning is or immoral” (p. 235). There is however a third possibility closer to the truth: Bok’s facts and conclusions both could be flawed. Bok’s indictment boils down to the following themes: JOURNAL OF APPLIED ANIMAL WELFARE SCIENCE, 5(3), 243–246 Copyright