HUMAN GENE THERAPY: DOWN THE SLIPPERY SLOPE?

The strength of a slippery slope argument is a matter of some dispute. Some see it as a reasonable argument pointing out what probably or inevitably follows from adopting some practice, others see it as essentially a fallacious argument. However, there seems to be a tendency emerging to say that in many cases, the argument is not actually fallacious, although it may be unsubstantiated. I shall not try to settle this general discussion, but merely seek to assess the strength of the slippery slope argument applied to human gene therapy. The structure of my argument will be the following. First, I shall distinguish between three different versions of the slippery slope argument; two logical versions and an empirical one. Next, I will address human gene therapy in terms of each of the three versions, partly relying on slippery slope arguments against this practice that have already surfaced in the literature. I shall argue that neither version pulls through. The logical versions fail primarily because relevant distinctions can be made between different uses of gene therapy, contrary to what the proponents of the arguments claim. The empirical version fails because there seems to be no evidence supporting the claim that we shall in fact slide down the slope if we engage in gene therapy, and because if we accepted the conclusion that we should not allow gene therapy on the basis of the empirical argument, we should have to make very far-reaching and undesirable modifications in health care in general, in order to be consistent. Or at least so I shall argue.     

The argument from intrinsic value: a critique

In his recent book Abortion and Unborn Human Life , Patrick Lee develops an argument for foetal personhood based on intrinsic value. Lee argues that since the foetus is identical with the rational, self-conscious being who will exist a few years later, and since this rational, self-conscious being indisputably is intrinsically valuable, therefore the foetus must already be intrinsically valuable; for nothing can come to be at one time but become intrinsically valuable at another. I show that this argument fails on two counts. First, the crucial premise that a thing's intrinsic value must derive from its essential properties is question-begging and devoid of support. Second, that premise is inconsistent with the pro-life position.     

The Principle of Procreative Beneficence: Old Arguments and A New Challenge

In the last ten years, there have been a number of attempts to refute Julian Savulescu's Principle of Procreative Beneficence; a principle which claims that parents have a moral obligation to have the best child that they can possibly have. So far, no arguments against this principle have succeeded at refuting it. This paper tries to explain the shortcomings of some of the more notable arguments against this principle. I attempt to break down the argument for the principle and in doing so, I explain what is needed to properly refute it. This helps me show how and why the arguments of Rebecca Bennett, Sarah Stoller and others fail to refute the principle. Afterwards, I offer a new challenge to the principle. I attack what I understand to be a fundamental premise of the argument, a premise which has been overlooked in the literature written about this principle. I argue that there is no reason to suppose, as Savulescu does, that morality requires us to do what we have most reason to do. If we reject this premise, as I believe we have reason to do, the argument for Procreative Beneficence fails.     

The impairment argument for the immorality of abortion revisited

Eric Vogelstein has defended Don Marquis' ‘future-like-ours' argument for the immorality of abortion against what is known as the Identity Objection, which contends that for a fetus to have a future like ours, it must be numerically identical to an entity like us that possesses valuable experiences some time in the future. On psychological accounts of personal identity, there is no identity relationship between the fetus and the entity with valuable experiences that it will become. Vogelstein maintains that a non-sentient fetus nonetheless has a future like ours because it is numerically identical with a future organism that has a mind that bears valuable experiences. Skott Brill, drawing on Jeff McMahan's embodied mind account, denies that human organisms directly have experiences, claiming that they only have experiences derivatively by virtue of their thinking part, and the loss of a future like ours is not transferred to the organism. I show that on McMahan's account, a strong case can be made for the organism having experiences directly, and the subject having these experiences derivatively. This negates Brill's reasoning, although it does imply that non-sentient fetuses do not have a future like ours in quite the same way as we do. I conclude that this is not problematic for Marquis' argument.     

‘The Miserablest People in the World’: Race,Humanism and the Australian Aborigine

This paper considers how an idea of the Australian Aborigine impacted upon the development of racial thinking throughout the nineteenth century. We distinguish three phases of this development. Against the background of what was considered to be a distinctly human capacity to rise above nature, our central argument however is that the extreme and irremediable savagery attributed to the Aborigine led to the mid‐nineteenth shift to a polygenist, or an innatist, idea of race. The first part of our discussion, covering the early 1800s, elicits a specifically humanist puzzlement at the unimproved condition of the Aborigines. But, as we will show in the central part of our discussion, it was not only the Aborigines' inclination but their capacity for ‘improvement’ that came to be doubted. Challenging the very basis upon which ‘the human’ had been defined, and the unity of humankind assumed, the Aborigine could not be accommodated within a prevailing conception of racial difference as a mere variety of the human. The elaboration of polygenism may therefore be understood as arising out of this humanist incomprehension: as an attempt to account for the ontologically inexplicable difference of the Australian Aborigine. In the final part of our discussion, we trace the legacy of the Aborigine's place within polygenism through the evolutionary thought of the late nineteenth century. Despite an explicit return to monogenism, here the Aborigine is invoked to support the claim that race constitutes a more or less permanent difference and, for certain races, a more or less permanent deficiency. And as, in these terms, the anomalous Aborigine became an anachronism, so Australia's indigenous peoples came to embody the most devastating conclusion of evolutionary thought: that in the human struggle for existence certain races were destined not even to survive.     

Evolutionary contingency and SETI revisited

The well-known argument against the Search for ExtraTerrestrial Intelligence (SETI) due to George Gaylord Simpson is re-analyzed almost half a century later, in the light of our improved understanding of preconditions for the emergence of life and intelligence brought about by the ongoing “astrobiological revolution”. Simpson’s argument has been enormously influential, in particular in biological circles, and it arguably fueled the most serious opposition to SETI programmes and their funding. I argue that both proponents and opponents of Simpson’s argument have occasionally mispresented its core content. Proponents often oversimplify it as just another consequence of biological contingency, thus leaving their position open to general arguments limiting the scope of contingency in evolution (such as the recent argument of Geerat Vermeij based on selection effects in the fossil record). They also tend to neglect that the argument has been presented as essentially atemporal, while referring to entities and processes that are likely to change over time; this has become even less justifiable as our astrobiological knowledge increased in recent years. Opponents have failed to see that the weaknesses in Simpson’s position could be removed by restructuring of the argument; I suggest one way of such restructuring, envisioned long ago in the fictional context by Stanislaw Lem. While no firm consensus has emerged on the validity of Simpson’s argument so far, I suggest that, contrary to the original motivation, today it is less an anti-SETI argument, and more an astrobiological research programme. In this research programme, SETI could be generalized into a platform for testing some of the deepest assumptions about evolutionary continuity and the relative role of contingency versus convergence on unprecedented spatial and temporal scales.     

Essential properties and the right to life: a response to Lee

In 'The Pro-Life Argument from Substantial Identity: A Defence', Patrick Lee argues that the right to life is an essential property of those that possess it. On his view, the right arises from one's 'basic' or 'natural' capacity for higher mental functions: since human organisms have this capacity essentially, they have a right to life essentially. Lee criticises an alternative view, on which the right to life arises from one's 'developed' capacity for higher mental functions (or development of some other accidental property). I argue that his criticisms of this alternative view are misguided or self-defeating, and that there are good reasons to hold we have a right to life accidentally rather than essentially.     

Marquis: A Defense of Abortion?

This is a reply to Don Marquis'Why Abortion is Immoral.' Marquis, who asserts that abortion is morally wrong, bases his argument on the following premise: Killing a being is morally wrong if that being is the sort of being who has a valuable future. I argue that this premise is false. I then assert that if I am correct about this premise being false, Marquis is faced with a dilemma. If he does not alter the premise in a way that makes it true, his argument is unsound. However, if he does make such an alteration, he must also alter a second premise in his argument, and this second change opens him to the charge of question begging. In addition, I conclude that such an alteration requires Marquis to adopt a position much like that taken by Judith J. Thompson in 'A Defense of Abortion,' a position he initially states is indefensible.     

Reconsidering cochlear implants: the lessons of Martha's Vineyard

I distinguish and assess three separate arguments utilized by the opponents of cochlear implants: that treating deafness as a medical condition is inappropriate since it is not a disability; that so treating it sends a message to the Deaf that they are of lesser worth; and that the use of such implants would signal the end of Deaf culture. I give some qualified support to the first and second claim, but find that the principal weight of the argument must be borne by the third argument: that use of the cochlear implants is impermissible because Deaf culture is intrinsically valuable. I show that this claim is, in practice, incompatible with the claim that deafness is not a disability: that the significant disadvantages suffered by the hearing impaired can only be corrected by measures that would end Deaf culture. Since the potential recipients of cochlear implants are, in the main, the prelingually deaf children of hearing parents, the burden of banning the implants would be borne by people who are not members of Deaf culture, and who owe that culture nothing over and above what we all owe cultures in general. I conclude that we cannot ask the parents of these children to sacrifice the interests of their children for the sake of Deaf culture.     

Two puzzles for Marquis's conservative view on abortion

Don Marquis argues that abortion is morally wrong in most cases since it deprives the fetus of the value of its future. I criticize Marquis’s argument for the modified conservative view by adopting an argumentative strategy in which I work within his basic account: if it is granted that his fundamental idea is sound, what follows about the morality of abortion? I conclude that Marquis is faced with a dilemma: either his position must shift towards the extreme conservative view on which abortion is never morally permissible, or he must abandon any recognizably conservative view. This dilemma suggests that Marquis’s view is either deeply implausible or that he cannot use this argument to successfully support his preferred position.     

Dutch Protocols for Deliberately Ending the Life of Newborns: A Defence

The Groningen Protocol, introduced in the Netherlands in 2005 and accompanied by revised guidelines published in a report commissioned by the Royal Dutch Medical Association in 2014, specifies conditions under which the lives of severely ill newborns may be deliberately ended. Its publication came four years after the Netherlands became the first nation to legalize the voluntary active euthanasia of adults, and the Netherlands remains the only country to offer a pathway to protecting physicians who might engage in deliberately ending the life of a newborn (DELN). In this paper, I offer two lines of argument. The first is a positive argument for the Protocol, grounded in the good of the newborn as unanimously determined by those in a position to determine it. The second addresses the widely shared belief that the killing of newborns is morally prohibited, where I offer two arguments—one grounded in the fact that the kinds of cases the Protocol is meant to govern are very rare and highly unusual, and the other focused more broadly on the role of pre-theoretical beliefs in moral reasoning—meant to undermine the strong role that the critic of the Protocol affords this belief. I argue that, given this second line of argument, the beliefs underlying my positive argument for the Protocol are in fact more secure than the widely shared belief underlying the critic’s position.     

How developmental is evolutionary developmental biology?

Evolutionary developmental biology (evo-devo) offers both an account of developmental processes and also new integrative frameworks for analyzing interactions between development and evolution. Biologists and philosophers are keen on evo-devo in part because it appears to offer a comfort zone between, on the one hand, what some take to be the relative inability of mainstream evolutionary biology to integrate a developmental perspective; and, on the other hand, what some take to be more intractable syntheses of development and evolution. In this article, I outline core concerns of evo-devo, distinguish theoretical and practical variants, and counter Sterelny's recent argument that evo-devo's attention to development, while important, offers no significant challenge to evolutionary theory as we know it. This revised version was published online in July 2006 with corrections to the Cover Date.     

The cultural construction of gendered bodies: Biology and metaphors of production and destruction*

One way of conceiving of the anthropological task is that of countering the degradations and “dehumanizations” of the “other” to which the species is prone by promoting “transcendent humanization.” However efficiently and professionally anthropologists gather their materials and form them into their ethnographic and ethnologic analyses, may not this “ethical impulse” be postulated as the “final cause” of our efforts? But what could such a sonorous phrase mean ? And what is its relationship to the systematic study of the “differences that make or do not make a difference” in culture to which anthropology has long been devoted? I will argue that it involves a dynamic of categories and that this dynamic is itself an object of systematic study. Recently, for example, some anthropologists have been writing “against culture,” seeing the culture concept and associated theory more as barriers than as benefits to pan‐human understanding. I will argue that this is an instance of “transcendent humanization.” One cannot but be sympathetic to the thrust and merits of this argument. But at the same time one wants to ask what implications it holds for the systematic study and understanding of the other. This article, then, examines some elementary vectors in the “dynamic of the categorical” involved in these and related recent debates which also may be seen in terms of transcendence and humanization: the debate over relativism and the recently emergent debate over “enlightenment mythmaking” in anthropology.     

Addiction,Voluntary Choice,and Informed Consent: A Reply to Uusitalo and Broers

In an earlier article in this journal I argued that the question of whether heroin addicts can give voluntary consent to take part in research which involves giving them a choice of free heroin does not – in contrast with a common assumption in the bioethics literature – depend exclusively on whether or not they possess the capacity to resist their desire for heroin. In some cases, circumstances and beliefs might undermine the voluntariness of the choices a person makes even if they do possess a capacity for self‐control. Based on what I took to be a plausible definition of voluntariness, I argued that the circumstances and beliefs typical of many vulnerable heroin addicts are such that we have good reasons to suspect they cannot give voluntary consent to take part in such research, even assuming their desire for heroin is not irresistible. In a recent article in this journal, Uusitalo and Broers object to this on the grounds that I misdescribe heroin addicts' options set, that the definition of voluntariness on which I rely is unrealistic and too demanding, and, more generally, that my view of heroin addiction is flawed. I think their arguments derive from a misunderstanding of the view I expressed in my article. In what follows I hope therefore to clarify my position.     

Dimensions of rationing: who should do what?

Priority setting is a complex interaction of multiple decisions at various levels in the organisation and constrained by history. There is no self evident set of ethical principles or analytical tools to determine what decisions we should take at various levels, nor is there an obvious or easy way to resolve the clash of claims on resources. To make priority setting more "rational" we should concentrate on the processes and structure of decision making and the relation of macro and micro decisions. The debate should promote reasoned, informed, and open argument, draw on a variety of perspectives, and involve a plurality of interests. The aim must be to build up, over time, the capacity to engage in continuous, collective argument.     

Altruistic surrogacy and informed consent

A crucial premise in many recent arguments against the moral permissibility of surrogate motherhood arrangements is the claim that a woman cannot autonomously consent to gestating and relinquishing a child to another couple, because she cannot be fully informed about what her future emotional responses will be to the foetus developing within her, and to the giving up of the newborn infant to its social parents. When conjoined with some moral principle about the justifiable limits on the ways others can be expected to exercise their autonomy on our behalf, this claim is often taken to establish that various forms of surrogate motherhood arrangements are morally wrong. In this paper I want to show that there is a serious non sequitur in this kind of argument. That is, I want to show that even if women cannot in fact have this kind of information about what their future emotional responses to pregnancy and relinquishment will be, nothing follows about the wrongness or otherwise of surrogacy. For, when we consider what counts as informed consent in the context of other important ventures with uncertain consequences, it becomes clear that informed consent does not require having this kind of information about one's future emotional states. In putting these arguments, I also hope to clarify some of the connections which might be thought to hold between informed consent and autonomous decision-making generally.     

Does consciousness overflow cognitive access? Novel insights from the new phenomenon of attribute amnesia

The moment we open our eyes, we experience a rich and detailed visual world, but the amount of information available to report is rather limited. This dissociation relates to a major debate regarding the nature of visual consciousness. The overflow argument suggests that our conscious experience is quite rich and far beyond what can be reported, standing in sharp contrast to the nooverflow argument that visual consciousness is severely impoverished and limited to what can be reported. In this paper, we systematically reviewed existing evidence in favor of the overflow argument, including studies of several variations of the iconic memory paradigm and the divided attention paradigm, as well as studies of neural correlates of consciousness. Simultaneously,we expounded some critical objections and alternative interpretations to such evidence, as well as some opposing evidence.Finally, we introduced a series of our recent studies based on a striking phenomenon of attribute amnesia, which we believe could provide new insight into the overflow view of visual consciousness.     

The determination of the best interests in relation to childhood immunisation

There are many different ethical arguments that might be advanced for and against childhood vaccinations. In this paper I explore one particular argument that focuses on the idea that such vaccinations are justifiable because they are held to be in the best interests of a particular child. Two issues arise from this idea. The first issue is how best interests are to be determined in this case. The second issue is what follows from this to justify potential interventions within the family in relation to such vaccinations. I argue that best interests must be characterised objectively in such situations and that this means that, in at least some cases, parental decision-making about vaccinating their children may be overridden.     

Identification of key amino acid residues that determine the ability of high risk HPV16-E7 to dysregulate major histocompatibility complex class I expression

High risk human Papillomavirus (HPV) types are the major causative agents of cervical cancer. Reduced expression of major histocompatibility complex class I (MHC I) on HPV-infected cells might be responsible for insufficient T cell response and contribute to HPV-associated malignancy. The viral gene product required for subversion of MHC I synthesis is the E7 oncoprotein. Although it has been suggested that high and low risk HPVs diverge in their ability to dysregulate MHC I expression, it is not known what sequence determinants of HPV-E7 are responsible for this important functional difference. To investigate this, we analyzed the capability to affect MHC I of a set of chimeric E7 variants containing sequence elements from either high risk HPV16 or low risk HPV11. HPV16-E7, but not HPV11-E7, causes significant diminution of mRNA synthesis and surface presentation of MHC I, which depend on histone deacetylase activity. Our experiments demonstrate that the C-terminal region within the zinc finger domain of HPV-E7 is responsible for the contrasting effects of HPV11- and HPV16-E7 on MHC I. By using different loss- and gain-of-function mutants of HPV11- and HPV16-E7, we identify for the first time a residue variation at position 88 that is highly critical for HPV16-E7-mediated suppression of MHC I. Furthermore, our studies suggest that residues at position 78, 80, and 88 build a minimal functional unit within HPV16-E7 required for binding and histone deacetylase recruitment to the MHC I promoter. Taken together, our data provide new insights into how high risk HPV16-E7 dysregulates MHC I for immune evasion.