The Disclosure of Genetic Information: A Human Research Ethics Perspective

Increasing emphasis on genetic research means that growing numbers of human research projects in Australia will involve complex issues related to genetic privacy, familial information and genetic epidemiology. The Office of Population Health Genomics (Department of Health, Western Australia) hosted an interactive workshop to explore the ethical issues involved in the disclosure of genetic information, where researchers and members of human research ethics committees (HRECs) were asked to consider several case studies from an ethical perspective. Workshop participants used a variety of approaches to examine the complex ethical issues encountered, but did not consistently refer to the values and principles outlined in the National Statement on Ethical Conduct in Human Research (NHMRC 2007) or apply rational ethical approaches. Overall, the data suggested that both researchers and HREC members may benefit from further education and support regarding the application of ethical frameworks to the issues encountered in genetic research.     

Parasites, parasitology and parasitologists

The science of parasitology is one of the many new disciplines of the twentieth century, as such it is a dynamic and rapidly evolving science which encompasses an increasing number of sub-disciplines and technologies. However, will the fragmentation involved in current methods of scientific enquiry and the competition for funding mean the decline of certain areas of parasitology or perhaps the complete loss of the discipline. This paper attempts to address these questions by considering the development of the discipline of parasitology especially within Australia and by considering the mechanisms of attaining funding for science. Technological change and its impact on parasitology is also considered, and requirements for maintenance of the discipline and its practitioners are suggested.     

Comparing Non-Medical Sex Selection and Saviour Sibling Selection in the Case of <Emphasis Type="Italic">JS and LS v Patient Review Panel: Beyond the Welfare of the Child?</Emphasis>

The national ethical guidelines relevant to assisted reproductive technology (ART) have recently been reviewed by the National Health and Medical Research Council (NHMRC). The review process paid particular attention to the issue of non-medical sex selection, although ultimately, the updated ethical guidelines maintain the pre-consultation position of a prohibition on non-medical sex selection. Whilst this recent review process provided a public forum for debate and discussion of this ethically contentious issue, the Victorian case of JS and LS v Patient Review Panel (Health and Privacy) [2011] VCAT 856 provides a rare instance where the prohibition on non-medical sex selection has been explored by a court or tribunal in Australia. This paper analyses the reasoning in that decision, focusing specifically on how the Victorian Civil and Administrative Tribunal applied the statutory framework relevant to ART and its comparison to other uses of embryo selection technologies. The Tribunal relied heavily upon the welfare-of-the-child principle under the Assisted Reproductive Treatment Act 2008 (Vic). The Tribunal also compared non-medical sex selection with saviour sibling selection (that is, where a child is purposely conceived as a matched tissue donor for an existing child of the family). Our analysis leads us to conclude that the Tribunal’s reasoning fails to adequately justify the denial of the applicants’ request to utilize ART services to select the sex of their prospective child.     

Unequal protection for patient rights: The divide between university and health ethics committees

Despite recommendations from the Cartwright Report ethical review by health ethics committees has continued in New Zealand without health practitioners ever having to acknowledge their dual roles as health practitioners researching their own patients. On the other hand, universities explicitly identify doctor/research-patient relations as potentially raising conflict of role issues. This stems from the acknowledgement within the university sector itself that lecturer/research-student relations are fraught with such conflicts. Although similar unequal relationships are seen to exist between health resarchers and their patients, the patient/subjects are not afforded the levels of protection that are afforded student/subjects. In this paper we argue that the difference between universities and health research is a result of the failure of the Operational Standard Code for Ethics Committees to explicitly acknowledge the vulnerability of the patient and conflict of interests in the dual roles of health practitioner/researcher. We end the paper recommending the Ministry of Health consider the rewriting of the Operational Standard Code for Ethics Committees, in particular in the rewriting of section 26 of the Operational Standard Code for Ethics Committees. We also identify the value of comparative ethical review and suggest the New Zealand's Health Research Council's trilateral relationship with Australia's NHMRC (National Health and Medical Research Council) and Canada's CIHR (Canadian Institute of Health Research) as a useful starting point for such a process.     

Distinguishing between Directed and Undirected Cell Motility within an Invading Cell Population

Cell invasion is the basis of several fundamental biological systems including developmental morphogenesis and disease progression. Invasion processes involve combined cell motility and proliferation. Standard experimental approaches to characterize invasion systems focus on measuring population-level wavespeed data. However, continuum models which incorporate either directed or undirected motility both give rise to traveling wave solutions with a well-defined wavespeed in terms of the motility parameters. Therefore, such population-level models and experimental data cannot be used to determine whether the motility is directed or undirected. This is a major impediment limiting our ability to interpret experimental observations of cell invasion. We demonstrate how to overcome this difficulty using individual-level data and discrete models. This approach can be used to interpret and design time-lapse imaging data to determine whether the cell motility is directed or undirected. Making a distinction between directed and undirected motility has profound implications regarding our ability to design strategies to manage development and disease associated with cell invasion. The authors gratefully acknowledge the support from the Australian Research Council (ARC) Discovery Project DP0662804. MS is an ARC postdoctoral fellow, KL is an ARC professorial fellow.     

REVIEWS

Book reviewed in this article:
"The Biological Control of Prickly Pear in Australia." By A. P. D odd . Council for Sci. and Indus. Res. Bull .
Statistical Methods for Research Workers . By R. A. F isher .     

Molecular vaccines against parasites

Prophylactic vaccines can be expected to be one of the major practical outputs of parasitology research. Various groups within Australia have pursued the vaccine objective for several years, with particular emphasis on blood-stage falciparum malaria in man, intestinal helminths of sheep and cattle, cutaneous myiasis (blowfly strike) in sheep, cysticercosis in sheep and cattle, bovine babesiosis, and cattle ticks. Other vaccine programmes are concerned with giardiasis, filariasis, toxoplasmosis, fascioliasis, coccidiosis in poultry, cutaneous leishmaniasis and schistosomiasis japonica. For many years, the only available vaccine against a parasite in Australia has been the attenuated Babesia bovis vaccine produced by the Tick Fever Research Centre of the Queensland Department of Primary Industries. Strategies for achieving molecular vaccines are generally similar within the various research groups. They involve analysis of the immunology and immunochemistry of a model or in-vitro system; development of functional monoclonal antibodies; analysis of antibody specificities in clinically and/or functionally defined polyclonal sera; screening of cDNA or genomic expression libraries; peptide synthesis; identification of an appropriate vaccination schedule involving adjuvants or new recombinant DNA-based antigen delivery systems. Outlined below are five of the major vaccine programmes.     

Western Notions of Informed Consent and Indigenous Cultures: Australian Findings at the Interface

Despite the extensive consideration the notion of informed consent has heralded in recent decades, the unique considerations pertaining to the giving of informed consent by and on behalf of Indigenous Australians have not been comprehensively explored; to the contrary, these issues have been scarcely considered in the literature to date. This deficit is concerning, given that a fundamental premise of the doctrine of informed consent is that of individual autonomy, which, while privileged as a core value of non-Indigenous Australian culture, is displaced in Indigenous cultures by the honouring of the family unit and community group, rather than the individual, as being at the core of important decision-making processes relating to the person. To address the hiatus in the bioethical literature on issues relating to informed consent for Aboriginal peoples, the following article provides findings from a two-year research project, funded by Australia’s National Health and Medical Research Council (NHMRC), conducted in the Northern Territory. The findings, situated in the context of the literature on cultural safety, highlight the difference between the Aboriginal and biomedical perspectives on informed consent.     

New draft code for research involving humans proved a major challenge.

A new draft code of conduct for research involving humans aims to bring a fresh vision to the ethics field. The code is a joint endeavour of the Medical Research Council, the Natural Sciences and Engineering Research Council and the Social Sciences and Humanities Research Council and supersedes all three agencies'' earlier ethics statements. Once the draft code is revised and approved, likely by the end of the year, investigators will have a more refined understanding of the ethical limits of acceptable research.     

Cytoplasmic fibres associated with streaming and saltatory-particle movement in Heracleum mantegazzianum

Summary The giant cells of the petiolar hairs of Heracleum mantegazzianum contain cytoplasmic fibres that are readily visible with phase contrast or interference contrast optics. These fibres are associated with saltatory particle movement and protoplasmic streaming in this cell and are believed to be the living image of similar fibres reported in electron micrographs of a variety of cell types.This work is supported by grants from the Australian Research Grants Committee and the Reserve Bank of Australia (to T. P. O'Brien) and by a grant from the National Research Council of Canada (to M. E. McCully).     

Design of the Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial [ISRCTN19943732]

The Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial is a multicentre,randomised, placebo-controlled trial of magnesium sulphate (MgSO₄) funded by the UK Medical Research Council. When complete, it will be the largest single neuroprotective study undertaken to date. Conscious patients presenting within 12 h of acute stroke with limb weakness are eligible. The primary outcome measure is combined death and disability as measured using the Barthel Index at 90-day follow up. By randomizing 2700 patients, the study will have 84% power to detect a 5.5% absolute reduction in the primary end-point. By April 2000, 86 centres were participating, with representation in Canada, USA, Europe, South America, Singapore and Australia. So far, 1206 patients have been randomised, of whom 37% were treated within 6 h. Overall 3-month mortality was 20% and the primary outcome event rate was 43%. The study is ongoing and centres worldwide are encouraged to participate.     

Mathematical analysis of optimal multichannel filtering for nerve signals

This paper extends recent analyses (Roberts and Hartline, 1975; Ouztöreli and Stein, 1977) of optimal linear filters for separating neural signals from more than one electrode site. Roberts and Hartline's result, using a matched filter criterion, represents one of a class of optimal filters with different, but symmetrical, output waveforms derived by Ouztöreli and Stein (1977). Another narrow bandwidth filter of this class will give the optimal results according to an energy criterion, but may be less useful in practical situations.This work was partially supported by the Medical Research Council of Canada (Grant MRC-MT3307), the Technical Research Council of Denmark (Grant 516-6703 E406) and the National Research Council of Canada (Grant NRC A-4345)     

Use of INFIC data base for amino acid requirement studies

The International Network of Feed Information Centers (INFIC) database contains amino acid profiles of over 15000 feedstuffs prepared by various techniques by the countries of the world. Preliminary filtering of appropriate feedstuffs which might be used in fish feed formulations has generated a data base of over 100 commonly used ingredients. Many of these have digestibility coefficients for protein and some have amino acid digestibility coefficients listed. The data base is faulted by the variety of techniques used to measure amino acid profiles, and by many ingredients which have not had digestibility coefficients for the protein component determined. This data base is now being re-examined by the National Research Council to generate more exact values for the indispensable and dispensable amino acids present in feedstuffs. It is anticipated that the base will be further improved by cooperating laboratories specifically interested in amino acid profiles of various fish feed formulas. Regardless of these deficiencies, the existing INFIC data base and the scheduled improved one should provide fish feed formulae, chemical amino acid profiles, for least cost and for research diet functions. These data will form a first proximation for satisfying dietary requirements for various fish species used in nutritional requirement studies.     

Adenine phosphoribosyltransferase: A simple spectrophotometric assay and the incidence of mutation in the normal population

The significance of partial deficiency of erythrocyte adenine phosphoribosyltransferase (APRT), reported in a number of subjects with gout, has been investigated by studying its incidence in 700 normal blood donors. Three clearly deficient subjects were found, an incidence not significantly different from that in patients with abnormalities of urate metabolism. A new assay method for APRT is described in which an erythrocyte lysate is incubated with adenine and phosphoribosylpyrophosphate (PRPP) for a given time; both hemoglobin and adenine nucleotide (AMP) are then precipitated with lanthanum phosphate; the change in absorbance of adenine at 260 nm reflects the extent of its conversion to AMP by APRT.This work was supported by the National Health and Medical Research Council of Australia.     

A strategic plan for an Australian Long‐Term Environmental Monitoring Network

Because of the urgent need for robust, long‐term information on biodiversity loss and environmental change, we have proposed a Long‐Term (>10 years) Environmental Monitoring (LTEM) Network for Australia. The LTEM Network would comprise 25 Nodes distributed throughout Australia, be focused on terrestrial, inland aquatic and coastal estuarine ecosystems, and be established to monitor long‐term biodiversity loss and ecological change (patterns and trends). The LTEM Network would be question‐problem‐process‐driven and not infrastructure‐driven. Thus, the different Nodes in the LTEM Network would explicitly recognize different biota, different environmental problems, different environmental threats and different kinds of management interventions in different ecosystems. We provide a governance structure for the proposed LTEM Network and envisage that it would be characterized by being: (i) lean, yet powerful, agile and adaptive; (ii) both centralized (through a coordinating role by a Federal Government agency), yet decentralized in terms of where the Nodes are located and how they are operated and managed; and (iii) not overly bureaucratic. We also argue that it would be highly cost‐effective; our estimated cost for the establishment of an LTEM Network is $28 million per year or less than 0.25% of the total annual governmental expenditure of $12 billion on environmental management in 2003/2004. The LTEM Network would be a critical part of Australia's environmental infrastructure and provide the Nation, for the first time, with a formal, coordinated, long‐term Network to gauge status and change of biodiversity and environmental condition. We argue that this would allow the Nation to begin to address seriously many of the major data‐related deficiencies that currently exist in the environment and biodiversity conservation sectors in Australia.     

Gap junctions in human sebaceous glands

Summary An examination of human sebaceous glands by transmission electron microscopy has revealed the presence of gap junctions. The junctions are found in abundance between differentiating cells, and annular forms are also seen. The possible significance of this new finding is briefly discussed.We thank the ENT consultant staff of Royal Prince Alfred Hospital, Sydney, for making tissue available. The co-operation of the director, Dr. D.J.H. Cockayne, and staff of the University of Sydney Electron Microscope Unit is gratefully acknowledged. Mr. E. Foster provided excellent assistance with the photography. -The project was supported by the Consolidated Medical Research Funds, University of Sydney, and the National Health and Medical Research Council of Australia. One of us (N.K.) was the recipient of the Phyllis Anderson Medical Research Fellowship awarded by the Faculty of Medicine, University of Sydney     

Use of diathermy for weeding heterogeneous tissue cultures

Summary Cultures generated from tissues consisting of multiple types of cells are often heterogeneous. Unless the cell type of interest has or can be given some selective growth advantage it may be overgrown by other cells. While developing techniques for the tissue culture of microvascular endothelial cells we evaluated an electrosurgical generator (diathermy) to selectively kill nonendothelail cells. Primary cell cultures were observed at ×100 magnification under phase contrast microscopy and a needle electrode apposed to the cell to be destroyed. A return electrode was constructed by placing a sterile clip in contact with the culture medium. The diathermy power setting controlled the area of lysis. Use of this technique allowed weeding of unwanted cells without damage to endothelial cells, which were able to grow to confluence in pure culture. Dr. Marks receives a Medical Postgraduate Research Scholarship from the National Health and Medical Research Council of Australia. Financial support was received from the Leo Leukaemia and Cancer Research Trust and the Scleroderma Association of New South Wales.     

The location and phenotype of proliferating neural-crest-derived cells in the developing mouse gut

Neural crest cells that originate in the caudal hindbrain migrate into and along the developing gastrointestinal tract to form the enteric nervous system. While they are migrating, neural-crest-derived cells are also proliferating. Previous studies have shown that the expression of glial-derived neurotrophic factor (GDNF) and endothelin-3 is highest in the embryonic caecum, and that GDNF alone or in combination with endothelin-3 promotes the proliferation of enteric neural-crest-derived cells in vitro. However, whether neural proliferative zones, like those in the central nervous system, are found along the developing gut is unknown. We used a fluorescent nucleic acid stain to identify dividing cells or BrdU labelling (2 h after administration of BrdU to the mother), combined with antibodies specific to neural crest cells to determine the percentage of proliferating crest-derived cells in various gut regions of embryonic day 11.5 (E11.5) and E12.5 mice. The rate of proliferation of crest-derived cells did not vary significantly in different regions of the gut (including the caecum) or at different distances from the migratory wavefront of vagal crest-derived cells. The phenotype of mitotic enteric crest-derived cells was also examined. Cells expressing the pan-neuronal markers, neurofilament-M and Hu, or the glial marker, S100b, were observed undergoing mitosis. However, no evidence was found for proliferation of cells expressing neuron-type-specific markers, such as nitric oxide synthase (at E12.5) or calcitonin gene-related peptide (at E18.5). Thus, for enteric neurons, exit from the cell cycle appears to occur after the expression of pan-neuronal proteins but prior to the expression of markers of terminally differentiated neurons.This work was supported by the Australian Research Council (DP0345298) and the National Health and Medical Research Council of Australia (Project grant 145628 and Senior Research Fellowship 170224).     

The European Research Council--a new opportunity for European science

The long-awaited European Research Council (ERC), which receives money from the research budget of the European Union and will finance fundamental science for Europe's scientists, has finally been established. With a focus on excellence, calls for both young and experienced scientists and an average budget of \[euro]1 billion per year, the ERC will have the opportunity to give basic research in Europe a significant boost.     

Low conductance states of a single ion channel are not ‘closed’

We have used a polymer-exclusion method to estimate the sizes of the high and low-conductance states of Staphylococcus aureus -toxin channels across planar lipid bilayers. Despite a >10-fold difference in conductance between high and low-conductance states, the size differs by <2-fold. We conclude that factors other than the dimensions have a strong influence on the conductance of -toxin channels. We also show that the high conductance state is destabilized by the presence of high molecular weight polymers outside the channel, compatible with the removal of channel water as the high conductance state shrinks to the low conductance state.We are grateful to Drs. D.T. Edmonds, A.A. Lev and V.A. Parsegian for fruitful discussion and to the Cell Surface Research Fund, the Science and Engineering Research Council, The Wellcome Trust, UNESCO (Molecular and Cellular Biology Network) and the National Academy of Sciences/National Research Council for financial support.