Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

Profoundly important ethical and political controversies turn on the question of whether biological life is an essential aspect of a human person, or only an extrinsic instrument. Lee and George argue that human beings are physical, animal organisms - albeit essentially rational and free - and examine the implications of this understanding of human beings for some of the most controversial issues in contemporary ethics and politics. The authors argue that human beings are animal organisms and that their personal identity (...) across time consists in the persistence of the animal organisms they are; they also argue that human beings are essentially rational and free and that there is a radical difference between human beings and other animals; criticize hedonism and hedonistic drug-taking; present detailed defenses of the prolife positions on abortion and euthanasia; and defend the traditional moral position on marriage and sexual acts. (shrink)

ABSTRACT This article defends the following argument: what makes you and I valuable so that it is wrong to kill us now is what we are (essentially). But we are essentially physical organisms, who, embryology reveals, came to be at conception/fertilisation. I reply to the objection to this argument (as found in Dean Stretton, Judith Thomson, and Jeffrey Reiman), which holds that we came to be at one time, but became valuable as a subject of rights only some time later, (...) in virtue of an acquired characteristic. I argue against this position that the difference between a basic, natural capacity and some degree of development of such a capacity is a mere difference in degree, that this position logically implies the denial of equal personal dignity, and that the selection of the required degree of development of a capacity is necessarily arbitrary. (shrink)

D. Alan Shewmon has advanced a well-documented challenge to the widely accepted total brain death criterion for death of the human being. We show that Shewmon's argument against this criterion is unsound, though he does refute the standard argument for that criterion. We advance a distinct argument for the total brain death criterion and answer likely objections. Since human beings are rational animals – sentient organisms of a specific type – the loss of the radical capacity for sentience involves a (...) substantial change, the passing away of the human organism. In human beings total brain death involves the complete loss of the radical capacity for sentience, and so in human beings total brain death is death. (shrink)

We argue that all human beings have a special type ofdignitywhich is the basis for (1) the obligation all of us have not to kill them, (2) the obligation to take their well‐being into account when we act, and (3) even the obligation to treat them as we would have them treat us, and indeed, that all human beings areequalin fundamental dignity. We give reasons to oppose the position that only some human beings, because of their possession of certain characteristics (...) in addition to their humanity (for example, an immediately exercisable capacity for self‐consciousness, or for rational deliberation), have full moral worth. What distinguishes human beings from other animals, what makes human beingspersonsrather thanthings, is their rational nature, and human beings are rational creatures by virtue of possessing natural capacities for conceptual thought, deliberation, and free choice, that is, the natural capacity to shape their own lives. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Aquinas on the Beginning and End of Human Life by Fabrizio AmeriniPatrick LeeAquinas on the Beginning and End of Human Life. By Fabrizio Amerini. Translated by Mark Henninger. Cambridge, Mass.: Harvard University Press, 2013. Pp. xxii + 260. $29.95 (cloth). ISBN: 978-0-674-07247-3.This book provides a comprehensive and textually grounded presentation of Thomas Aquinas’s teaching on embryology and an assessment of its bioethical implications. Despite (what I regard as) (...) some mistakes on the application of that teaching to contemporary embryological data, it is an invaluable sourcebook for Aquinas on this issue. At times, Amerini’s “aporetic” style makes for convoluted arguments, but it raises challenging questions and thus will assist anyone working through these issues. (As the title indicates, it also treats the end of life—but only very briefly, in a couple of pages near the end of the book.)The first two chapters examine Aquinas’s general principles regarding matter, form, and substantial generation (the coming to be of a substance), and his positon on the human soul as both subsistent and the substantial form of the human body. Amerini’s treatment is thorough and provides an extensive bibliographical guide to this issue. However, it seems to me that Amerini is less than clear on the distinctiveness of substantial change. Since there are (according to Aquinas and Aristotle) no degrees in the category of substance, generation is not a process but an instantaneous change. Amerini’s frequent use of the term “process of generation,” as well as the position he later proposes on the identity of the embryo, seems to conflict with that point. [End Page 489]Chapters 3 and 4 contain detailed exposition of Aquinas’s basic embryological position, and chapter 4 raises various questions about this position (including doubts that Amerini evidently has about the unicity of the human being’s substantial form). Applying his basic metaphysical principles to what he at the time believed were the embryological facts, Aquinas concluded that the human being with a rational soul is not present until forty days after fertilization for males or ninety days for females. The father and the mother generate the offspring, but the mother provides only the material cause in the form of menstrual blood; the father is the efficient and formal cause, acting through the semen as an instrumental cause. With the power (virtus) of the principal cause in it, the semen gradually organizes the menstrual blood provided by the mother to form, first, a being with a vegetative soul, then an animal, and finally an animal with a body suited to be formed by a rational soul, which God then infuses into it. Aquinas holds that, unlike a sensitive or vegetative soul, a rational soul must be directly created by God, since the rational soul is the source of operations that are independent of matter, that is, performed by the human being but without a bodily organ. Only matter that is suited to a form can receive it. Therefore the matter must be suitably disposed. Just as one can make a knife only with matter capable of supporting its function—and so the matter must be hard and capable of being sharp—so only a body with sense organs, and thus capable of supporting those actions prerequisite to rational operations, can receive a rational soul.Chapter 5 sets out in detail Amerini’s exposition and interpretation of Aquinas on the identity of the embryo. Amerini recognizes, of course, Aquinas’s mistakes and ignorance regarding basic embryological facts—inevitable given the time in which he wrote. Still, Amerini holds that Aquinas’s main conclusion regarding delayed hominization is still valid. He agrees with Aquinas that the general proportionality requirement implies that the embryo/fetus must first possess sensory organs to have a body apt for the reception of a rational soul.On the other hand, Amerini also advances what he believes is a via media between proponents of delayed hominization and proponents of immediate hominization. He argues that although the embryo is not numerically identical with the human being (which comes to be only with the infusion of the rational soul), nevertheless, the embryo from... (shrink)

In various places we have defended the position that a new human organism, that is, an individual member of the human species, comes to be at fertilization, the union of the spermatozoon and the oocyte. This individual organism, during the ordinary course of embryological development, remains the same individual and does not undergo any further substantial change, unless monozygotic twinning, or some form of chimerism occurs. Recently, in this Journal Jason Morris has challenged our position, claiming that recent findings in (...) reproductive and stem cell biology have falsified our view. He objects to our claim that a discernible substantial change occurs at conception, giving rise to the existence of a new individual of the human species. In addition, he objects to our claim that the embryo is an individual, a unified whole that persists through various changes, and thus something other than a mere aggregate of cells. Morris raises a number of objections to these claims. However, we will show that his arguments overlook key data and confuse biological, metaphysical, and ethical questions. As a result, his attempts to rebut our arguments fail. (shrink)

I develop and refine an argument for the total brain death criterion of death previously advanced by Germain Grisez and me: A human being is essentially a rational animal, and so must have a radical capacity for rational operations. For rational animals, conscious sensation is a pre-requisite for rational operation. But total brain death results in the loss of the radical capacity for conscious sensation, and so also for rational operations. Hence, total brain death constitutes a substantial change—the ceasing to (...) be of the human being. Objections are considered, including the objection that total brain death need not result in the loss of capacity for sensation, and that damage to the brain less than total brain death can result in loss of capacity for rational operations. (shrink)

ABSTRACT In this article, I reply to criticisms of Dean Stretton of the pro‐life argument from substantial identity. When the criterion for the right to life proposed by most proponents of the pro‐life position is rightly understood – being a person, a distinct substance of a rational nature – this position does not lead to the difficulties Stretton claims it does.

From the standpoint of a Christian philosopher, heeding the teaching and exhortations of Pope John Paul II and previous popes, I examine three directions in which the recent philosophical debate has developed. In the last seven or eight years there has been 1) a renewed focus on the biological issue of when a human individual comes to be, 2) new arguments for the proposition that personhood is a characteristic acquired after birth, and 3) refinements of the early argument of Judith (...) Thomson. Replying to these developments, I defend, on philosophical grounds, the pro-life position. I argue that a distinct, whole (though immature) human individual comes to be at conception, that he or she is a person, with full moral worth, from the moment he or she comes to be, and the mothers and fathers have a special responsibility to their children which entails (at least) that they ought not to choose to abort them. I conclude by briefly indicating, from the standpoint of Christian faith, why Christian philosophers should vigorously pursue this debate. (shrink)

I defend the position argued previously by Germain Grisez and me that total brain death is a valid criterion of death on the grounds that a human being is essentially a rational animal, and a brain-dead body lacks the radical capacity for rational actions. I reply to Josef Seifert’s objection that our positions rest on a reductionist view of the human person, and to other objections concerning the inter-relation between the human soul, its powers, and functions of the brain. I (...) argue that a brain-dead body lacks the material dispositions needed for having the form or soul of a human being. (shrink)

I reply to Steven Jensen’s article, “Phoenix Rising from the Ashes: Recent Attempts to Revive New Natural Law Action Theory,” which appeared in this journal in 2020. His arguments helpfully clarify where the disagreements between the strict and broad views of intention lie but, I argue, fail to refute the arguments and explanations he criticizes. I argue he misinterprets the strict view’s reference to necessity in its criterion for what is intended. I also argue against what he labels as the (...) “identity thesis,” and against his attempt to show that the strict view (or New Natural Law theory of action) leads to the absurdity that most acts of adultery are not actually adultery. (shrink)

In chapters 9 and 10 of their book Roman but Not Catholic, Kenneth Collins and Jerry Walls criticize the Roman Catholic positions on the Eucharist as a sacrifice and on the ministerial priesthood. I reply to their historical and theological objections, and defend the belief that the Eucharistic sacrifice, the Mass, is a re-presentation, or making present, of Jesus’s redemptive sacrifice on Calvary, and a key component in God’s incarnational strategy for redeeming us.

This book defends the conjugal view of marriage. Patrick Lee and Robert P. George argue that marriage is a distinctive type of community: the union of a man and a woman who have committed to sharing their lives on every level of their beings (bodily, emotionally, and spiritually) in the kind of union that would be fulfilled by conceiving and rearing children together. The comprehensive nature of this union, and its intrinsic orientation to procreation as its natural fulfillment, distinguishes (...) marriage from other types of community and provides the basis for the norms of marital exclusivity and permanence. Lee and George detail how the basic moral norms regarding sexual acts follow from the ethical requirement to respect the good of marriage and explain how the law should treat marriage, given its conjugal nature, examining both the same-sex-marriage issue and civil divorce. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:EXISTENTIAL PROPOSITIONS IN THE THOUGHT OF ST. THOMAS AQUINAS A REVALENT VIEW of St. Thomas Aquinas's position on the logic of propositions has been that according to him propositions of the :form, x is, hold a privileged place, that they are in a special sense " existential," and that such propositions straight.forwardly attribute the act of exi,stence to an individual or to a class of individuals.1 Some texts seem (...) to support such an interpretation. For example, in his commentary on Aristotle's Perihermeneias, Aquinas says: " To clarify this we must note that the verb 'is ' itself is sometimes predicated in an enunciation, as in ' Socrates is.' By this we intend to signify that Socrates really is." 2 This passage seems to treat the predicate " exists " or " is " as unproblematical, as though it had a straightforward meaning needing little clarification, at least in the context of a logical treatise. On the basis of such a text, one may be tempted to infer that for Aquinas " Socrates exists " has the same logical form as " Socrates sits," and that " Men exist " is of the same form as " Men are mortal.'' Peter Geach has shown, however, that Aquinas's doctrine here is not as simple as it may first appear. For Aquin,as some of the propositions which have the grammatical form of x is have 'a different logical form.3 Geach points out that for Aquinas the sentence, "Blindness exists," for example, actual1 E.g., Etienne Gilson, Being and Some Philosophers, 2nd ed. (Toronto: Pontifical Institute of Mediaeval Studies, 1952), 190-215. 2 Super Peri, Bk. II, lect. 2, # 212. Cf. Summa Contra Gentiles, Bk. II, ch. 37 at "FJ11J hoc..•." a Peter Geach, in P. T. Geach and G. E. M. Anscombe, Three Philosophers (New York: Cornell University, 1961), 88 ff; Peter Geach, "Form and Existence," in Aquinas: A Collection of Critical Essays, ed. A. Kenny (New York: Notre Dame U., 1969), pp. 41-47. 605 606 PATRICK LEE ly means, Something or other is blind. That is, blind is the real predicate rather than exists. Mo11eover, Geach argues, the logical peculiarity of this sentence is equally found in any sentence of the form, "an F exists." Such a proposition, " does not,attribute actuality (existence) to an F, but F-ness to something or other..." 4 And yet Geach will not apply rthis interpretation to all sentences of the form, " x is." He al'lgues that sentences in which " is " or " exists " is. joined to a logically pl'oper name are in a different category. Unlike in general propositions such as "an F exists," in such singular propositions, those using logically proper names, Geach,argues, actual existence is attributed to or predicated of an individual. "We have here a sense of 'is ' or 'exists ' that seems to me to be certainly a genuine predicate of individuals: the sense of ' exists ' in which one says that an individual came to exist, still exists, no longer exists, etc...."5 I believe that, while Geach's position is more accurate than the first interpretation, mentioned above, it is nevertheless still inaccurate on certain key points. While it is misleading to say that for Aquinas exists is never a genuine predicate; nevertheless, I will argue that it is his position that exists or existence is not a genuine predicate in any proposition which does not refer back to a previous proposition (or to what is known in or by previous propositional knowledge). Let us crull a proposition which refers to something known in a previous proposition a " second-order p11oposition," and one that does not thus refer a " first-order proposition." Then, I shall argue that for Aquinas exists is not a genuine predicate in any first-order proposition. Moreover, I believe that these points are crucial to understanding Aquinas's position on existence as well as his position on how knowledge is related,to reality, i.e., his realism. In this article I would like to examine Aquinas's thought on the logic of existential propositions and discuss its significance for epistemology. 4 Geach, " Form and Existence," Zoo. int., p. 45. 5 Ibid., p. 46. EXISTENTIAL PROPOSITIONS IN AQUINAS 607 In sections... (shrink)

I reply to an article in the ACPA Proceedings of 2001 by John Crosby in which he challenged the position that evil as such is a privation. Each of his arguments attempts to present a counterexample to the privation position. His first argument, claiming that annihilation is evil but not a privation, fails to consider that a privation need not be contemporaneous with the subject suffering the privation. Contrary to his second argument, I explain that the repugnance of pain is (...) consistent with its being good in the appropriate context. Against his third argument I contend that he mistakenly supposes that a choice’s being opposed to the good is incompatible with its being evil because of a disorder. I conclude by briefly reviewing one central argument for the privation position and contrast it with Crosby’s arguments, which, in addition to their other problems, fail to specify any intensional content, beyond repugnance in the case of pain, for the concept of evil. (shrink)

New natural law theory holds that the basic moral principles are prescriptions to pursue the goods to which our nature orients us. Since God is the author of our nature and intelligence, these moral principles are part of his plan for creation. These principles can be known prior to knowing that God exists and prior to knowing that they are in fact directives from him. Nevertheless, since God’s plan includes our active cooperation, morally good acts cooperate with God’s providence, and (...) morally bad acts substitute one’s subjective preference for God’s truth. Thus natural law principles direct us to a unified ultimate end, namely, the fulfillment of God’s plan. Therefore God and our relationship with him have a central place in NNLT. (shrink)

Tanzania’s Oldupai Gorge is a flagship human origins research destination, yet less recognised is that the Maasai inhabit the region. This thesis uses actor-network-theory to ethnographically compare palaeoanthropological and Maasai epistemology and ontology in Oldupai, and to understand why collaboration between the groups has been sporadic. Researchers and locals constructed knowledge in equally logical forms, combining established facts and artefacts with novel data to produce new facts and artefacts. Instead of fundamental epistemic disparities, the content of each group’s knowledge differed, (...) and this content was tied to subsistence strategies and culture. Scientists and the Maasai acquired resources in non-scientific and non-pastoral worlds to support their respective livelihoods, and multiplied ontologies by enacting composite – yet conflicting – versions of hybrid drought. Even though both groups dug in Oldupai, palaeoanthropological and Maasai subsistence exigencies have precluded meaningful collaboration. However, mutually beneficial partnerships are emerging in the birthplace of humanity. (shrink)

The problem addressed is: whether religious belief, defined here as accepting that God has revealed and that what he has revealed is true, could ever be rational. That is, does the idea of religious belief imply that it is irrational? The author attempts to resolve this problem in favor of religious belief, and suggests how reasons can legitimately function in religious belief. The evidentialist objection to religion is answered, and it is proposed that reasons might function, not to prove that (...) God has revealed, or that what he has revealed is true, but that the choice to believe is a morally responsible one. (shrink)

The reovirus cell attachment protein σ1 is a lollipopshaped structure with the fibrous tail anchored to the virion. Since it interacts with the cell receptor, σ1 is a major determinant of reovirus infectivity and tissue tropism. Studies on its structure‐function relationships have been facilitated by the fact that protein σ1 produced in any expression system is capable of binding to cell receptors. The use of site‐specific and deletion mutants has led to the identification and characterization of its virion anchorage and (...) receptor binding domains. Studies on the oligomeric status of σ1 have revealed that σ1 is a homotrimer and that two independent trimerization events at different loci (the N‐ and C‐terminal halves, respectively) of the protein, are involved in its generation. This also accounts for a clearly demonstrable dominant negative effect by a mutant subunit in a wild‐type/mutant σ1 heterotrimer. Current efforts are focused on the involvement of chaperones in the generation of σ1 and on events that take place upon σ1 binding to the cell receptor. Protein σ1 has therefore become an excellent model system for the study of both virus attachment and protein oligomerization and folding mechanisms. (shrink)