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Biomedical subjects

John Harris

Publications and source records attributed to John Harris.

At least 37 records · Page 2Linked to original sources
PubMed2005

Ethics and synthetic gametes.

The recent in vitro derivation of gamete-like cells from mouse embryonic stem (mES) cells is a major breakthrough and lays down several challenges, both for the further scientific investigation and for the bioethical and biolegal discourse. We refer here to these cells as gamete-like (sperm-like or oocyte-like, respectively), because at present there is still no evidence that these cells behave fully like bona fide sperm or oocytes, lacking the fundamental proof, i.e. combination with a normally derived gamete of the opposite sex to yield a normal individual. However, the results published so far do show that these cells share some defining features of gametes. We discuss these results in the light of the bioethical and legal questions that are likely to arise would the same process become possible with human embryonic stem (hES) cells.

Animals↗
PubMed2005

Sex selection and regulated hatred.

This paper argues that the HFEA's recent report on sex selection abdicates its responsibility to give its own authentic advice on the matters within its remit, that it accepts arguments and conclusions that are implausible on the face of it and where they depend on empirical claims, produces no empirical evidence whatsoever, but relies on reckless speculation as to what the "facts" are likely to be. Finally, having committed itself to what I call the "democratic presumption", that human freedom will not be constrained unless very good and powerful reasons can be produced to justify such infringement of liberty, the HFEA simply reformulates the democratic presumption as saying the opposite--namely that freedom may only be exercised if powerful justifications are produced for any exercise of liberty.

Child↗
PubMed2005

The moral status of the embryo post-Dolly.

Cameron and Williamson have provided a provocative and timely review of the ethical questions prompted by the birth of Dolly. The question Cameron and Williamson seek to address is "In the world of Dolly, when does a human embryo acquire respect?". Their initial discussion sets the scene by providing a valuable overview of attitudes towards the embryo, summarising various religious, scientific, and philosophical viewpoints. They then ask, "What has Dolly changed?" and identify five changes, the first being that fertilisation is no longer required to create an embryo. Following this analysis they then ask when an embryo created other than by fertilisation begins to acquire respect. This paper explores the ethical and legal issues highlighted by Cameron and Williamson's paper.

Animals↗
PubMed2004

Differential modulation of withdrawal reflexes by a cannabinoid in the rabbit.

Inhibition of spinal and trigeminal withdrawal reflexes by morphine and by the cannabinoid agonist HU 210 has been studied in anaesthetized and in decerebrated rabbits. In intact, pentobarbitone-anaesthetized animals, the jaw-depressor reflex (JDR) evoked by stimulation of the tongue, and the reflex elicited in the ankle flexor tibialis anterior (TA) by stimulation of the toes were inhibited to the same extent by morphine (1-30 mg kg(-1) i.v. cumulative). In spinalized, anaesthetized rabbits morphine depressed the JDR to the same level as in non-spinal preparations, but the effect of the opioid on the TA reflex was significantly reduced. All effects of morphine were reversed by naloxone (0.25 mg kg(-1), i.v.). In anaesthetised intact animals, HU 210 depressed the JDR at a dose of 100 nmol kg(-1) i.v. cumulative, reduced reflexes evoked in the knee flexor muscle semitendinosus (ST) by stimulation at the toes at a dose of 30 nmol kg(-1) i.v. cumulative, but had no consistent or significant effects on the TA reflex to toe stimulation. The same results were obtained in spinalized, anaesthetised animals. In decerebrated, spinalized rabbits with no anaesthesia, HU 210 (30 nmol kg(-1)) depressed both ST and TA reflexes evoked by toe stimulation. These data reveal that trigeminal and spinal withdrawal reflexes are equally sensitive to morphine provided the spinal cord is intact, suggesting that at least part of the action of systemic morphine is due to activation of descending inhibition. The present results also show for the first time that cannabinoid agonists can inhibit trigeminal withdrawal reflexes. HU 210 had differential effects on the three reflexes studied depending on the presence or absence of anaesthesia. This is the first occasion on which we have found pharmacological distinctions between withdrawal reflexes, and indicates that spinal sensorimotor processing is more heterogeneous than has been suspected previously.

Animals↗
PubMed2004

The organization of motor responses to noxious stimuli.

Withdrawal reflexes are the simplest centrally organized responses to painful stimuli, making them popular models for the study of nociception. Until recently, it was believed that withdrawal was a single reflex response involving excitation of all flexor muscles in a limb with concomitant inhibition of extensors. However, recent findings suggest that withdrawal reflexes are tailored to produce the most appropriate movement according the site at which the stimulus is applied, which could require extensors to act as the primary movers. This idea is supported by new evidence obtained from the direct measurement of limb movements, although these data indicate that differentiation of withdrawal reflexes is most readily seen from stimuli applied to the plantar surface of the foot. Injurious stimuli augment the protective function of reflexes by enhancing (sensitizing) reflexes that protect the injured site and inhibiting those reflexes that might exacerbate the insult. The areas from which a reflex can be sensitized closely match those from which the reflex itself can be evoked, provided that the spinal cord is intact. If descending pathways are interrupted, sensitization can be evoked from a much wider area. Thus, the exact movement made in a withdrawal reflex is determined by the location of the evoking stimulus and whether the reflex sensitized or inhibited after an injury depends on the relationship between the site of the injury and the movement made by the reflex. The factors should be borne in mind when designing experiments in which reflexes are used as the end point in studies of nociception.

Adaptation, Physiological↗
PubMed2004

5-HT receptors involved in opioid-activated descending inhibition of spinal withdrawal reflexes in the decerebrated rabbit.

The role of 5-HT(1B/1D), 5-HT(2) and 5-HT(3) receptors in mediating descending inhibition of spinal reflexes activated by application of fentanyl to the fourth ventricle has been studied in rabbits decerebrated under N(2)O/isoflurane anaesthesia. In the control state, intraventricular fentanyl (3-30 microg kg(-1)) depressed, to an equal extent, short- and long-latency reflexes in the medial gastrocnemius muscle nerve evoked by electrical stimulation of all sural nerve afferents. Inhibition of reflexes resulted from a decreased base line excitability in the reflex pathway accompanied by a reduction in the rate of temporal summation of responses. Fentanyl-induced suppression of short- and long-latency reflexes was significantly reduced after intrathecal administration of the selective 5-HT(2)-receptor antagonist ICI 170,809 (300 microg). The same dose of the selective 5-HT(1B/1D) blocker GR 127,935 reduced inhibition from intraventricular fentanyl only for long-latency reflexes (i.e. those parts of the response for which the afferent drive is provided mainly by Adelta and C-fibre afferents). The 5-HT(3) antagonist tropisetron (also 300 microg intrathecal) did not significantly alter the descending inhibition of reflexes evoked by fentanyl. Both GR 127,935 and tropisetron reduced temporal summation of reflexes per se, effects that were reversed by intraventricular fentanyl. These data suggest that the descending pathway(s) activated by intraventricular fentanyl liberate 5-HT in the spinal cord to inhibit withdrawal reflexes by acting at 5-HT(2) and 5-HT(1B/1D), but not 5-HT(3) receptors. 5-HT(1B/1D), and to a lesser extent 5-HT(3) receptors also appear to have a role in modulating temporal summation of reflexes evoked by repetitive stimuli.

Afferent Pathways↗
PubMed2004

Effects of the active neurosteroid allotetrahydrodeoxycorticosterone on long-term potentiation in the rat hippocampus: implications for depression.

We studied the effects of the active neurosteroid (ANS) allotetrahydrodeoxy corticosterone (ATHDOC) on long-term potentiation (LTP) in the dentate gyrus (DG) of intact, urethane anesthetized rats. Intravenous injection of the hormone at two doses, 0.1 and 0.5 mg/kg, produced a significant decrease in both components of the response: excitatory postsynaptic potentials (EPSP) and population spikes (PS). The effects were similar for the two doses. The results are discussed in terms of the potential mechanism by which ATHDOC modulates neural processes associated with symptoms present in depression syndromes.

Animals↗
PubMed2004

Genetic equity.

This paper proposes, elaborates and defends a principle of genetic equity. In doing so it articulates, explains and justifies what might be meant by the concept of 'human dignity' in a way that is clear, defensible and consistent with, but by no means the same as, the plethora of appeals to human dignity found in contemporary bioethics, and more particularly in international instruments on bioethics. We propose the following principle of genetic equity: humans are born equal; they are entitled to freedom from discrimination and equality of opportunity to flourish; genetic information may not be used to limit that equality.

Bioethics↗
PubMed2004

Immortal ethics.

This article draws on ideas published in my "Intimations of Immortality" essay in Science (Vol. 288, No. 5463, p. 59, April 7, 2000) and my "Intimations of Immortality-The Ethics and Justice of Life Extending Therapies" in editor Michael Freeman's Current Legal Problems (Oxford University Press 2002: 65-97). This article outlines the ethical issues involved in life-extending therapies. The arguments against life extension are examined and found wanting. The consequences of life extension are explored and found challenging but not sufficiently daunting to warrant regulation or control. In short, there is no doubt that immortality would be a mixed blessing, but we should be slow to reject cures for terrible diseases that may be an inextricable part of life-extending procedures even if the price we have to pay for those cures is increasing life expectancy and even creating immortals. Better surely to accompany the scientific race to achieve immortality with commensurate work in ethics and social policy to ensure that we know how to cope with the transition to parallel populations of mortals and immortals as envisaged in mythology.

Aged↗