Genomics reaches the clinic: from basic discoveries to clinical impact

Today, more than ever, basic science research provides significant opportunities to advance our understanding about the genetic basis of human disease. Close interactions among laboratory, computational, and clinical research communities will be crucial to ensure that genomic discoveries advance medical science and, ultimately, improve human health.     

The impossibility and necessity of quality of life research

There are probably a number of reasons why the medical community pays surprisingly little systematic attention to quality of life, either in research or in clinical care. Possibly our society's fascination with high technology and the rescue of endangered lives has encouraged the medical profession to focus on acute care, where their interventions can bring dramatic results. And perhaps because such high-tech acute care requires great knowledge and skill, medical educators have not devoted as much time to educating students and residents about the more mundane matters of medicine. Another reason, on which I will focus here, is the fact that scientific research into quality of life is particularly difficult, methodologically. It does not lend itself easily to the crisp, clean answers for which we strive in basic science. It is "soft," inexact, not "hard." In this article I hope to explain why such research is indeed fraught with hazard. The scientists are attempting a task that is, in a profound philosophical sense, impossible. They have no direct access to the data they most need, and every method of validating their results is fundamentally flawed. Nevertheless, I will also suggest how we can fruitfully undertake such research and, equally important, why we must.     

Marginalizing Experience: A Critical Analysis of Public Discourse Surrounding Stem Cell Research in Australia (2005�C6)

Over the past decade, stem cell science has generated considerable public and political debate. These debates tend to focus on issues concerning the protection of nascent human life and the need to generate medical and therapeutic treatments for the sick and vulnerable. The framing of the public debate around these issues not only dichotomises and oversimplifies the issues at stake, but tends to marginalise certain types of voices, such as the women who donate their eggs and/or embryos to stem cell research and the patients who might benefit from its potential clinical outcomes. This paper draws on empirical research conducted on a recent stem cell policy episode in Australia. From the qualitative examination of 109 newspaper opinion editorials and twenty-three in-depth interviews, it is argued that these voices are marginalised because they are based on discourses that have less epistemological status in public debate. Our results suggest that the personal experiences of women and patients are marginalised by the alliances that form between more powerful discourse communities that use science as a source of authority and legitimation. It is argued that members of these communities establish legitimacy and assert authority in public debate by discursively deploying science in claims that marginalise other epistemologies. Implications are discussed along with suggestions for a more enriched and inclusive public debate.     

Uncovering the biodiversity of genetic and reproductive systems: time for a more open approach. American Society of Naturalists E. O. Wilson Award winner address

Important scientific findings frequently arise from serendipitous findings. Unfortunately, many scientists are not prepared to take advantage of unexpected results and to question established paradigms, and this prevents them from capitalizing on their good fortune. In this essay, I first explain how pure serendipity led us to discover unusual modes of reproduction such as clonal reproduction by males and a green-beard gene. Next, I argue that the reproductive systems of ants and other organisms are probably much more diverse than is generally appreciated. This leads me to advocate for a new "molecular naturalist" approach to reproductive systems and a more "naturalistic" approach in population and evolutionary genetics. Finally, I make two further points. The first is that our current funding and education systems tend to hinder originality and curiosity. The other is that the field of ecology and evolution, and more generally all of science, would benefit from a shift in values from scientific productivity to scientific creativity. A few suggestions are made to this effect.     

Community medicine for clinicians in Canada: a recommendation for postgraduate training.

A large gap presently exists between the predominantly biologic expertise of the medical profession and the complex mixture of biologic, behavioural and epidemiologic components of health problems today. Furthermore, the development of community medicine in Canada has been relatively separate from that of the clinical disciplines. To enable clinicians to acquire the knowledge and skills to manage these health problems, much more community-oriented research, applied behavioural science and clinical epidemiology is needed within the clinical sector of medicine. I have proposed a definition of clinical community medicine and presented a strategy for training clinicians in community medicine skills that calls for administrators of clinical postgraduate programs to develop training in clinical community medicine. Residency programs in community medicine cannot be expected to provide such training given their nonclinical priorities, which focus mainly on the training of public health physicians.     

Medical fact and ulcer disease: a study in scientific controversy resolution

This study seeks to advance the understanding of controversy resolution in science. I take as a case study conceptualization and treatment of ulcer disease. Analysis of causal accounts and effective treatments illustrate the ways in which competing parallel research programs in medicine embody opposing social, political, and economic forces which are bound to the epistemological dimensions of scientific controversy (e.g., standards of evidence, reference, and inference), and which in turn shift perception of the burden of proof. The analysis illustrates the ways in which (1) medical diagnoses create as much as discover useful distinctions and (2) epistemic and non epistemic values divide scientists into competing research programs, as well as (3) the ways in which these structures often effectively prevent scientific controversy closure.     

Psychobiogeography: meanings of nature and motivations for a democratized conservation ethic

The language of ecosystem science is pervaded by value-laden terms such as pristine, fragile, disturbance, balance, dominance and alien species. Such terms have high status and are often used in the rhetoric of the conservation ethic. Here, I consider the possibility of the use of less value-laden terms such as change, increase, decrease and so on. This would distinguish between values and perceived trends or states and leave ecosystem science to deal with what is verifiable. However, I also consider the opposite point of view, in that the value-laden terms, like 'the balance of nature', relate to how a wide range of people feel about nature and are effective emotive motivators of the conservation ethic in society, providing a common language for a discourse between ecosystem scientists and other people.     

Teaming up: from motors to people

When I reflect on how I became a cell biologist and why I love being one today, one thing that comes to mind is the many terrific collaborations I have had. The science I am most proud of from my graduate and postdoctoral training would not have been possible without working in teams with other scientists. Now, in my own group, much of our best work is being done collaboratively, both within the lab and with other labs. In this essay, I will highlight my experiences working in teams as a trainee, the role teamwork has played in my own research group, and how important I think collaborative science is for the future of biological research.     

The Spatialisation of Disease: Foucualt and Evidence-based Medicine (EBM)

In this paper I draw on the French philosopher Michel Foucault for a viewpoint on aspects of EBM. This means that I develop his idea of the spaces occupied by disease. I give much of the paper to only one of these spaces, the space of perception of disease, in order to major on the medical gaze, one of Foucault’s best-known contributions to the philosophy of medicine. As I explain what I mean by each of the spaces of disease, I configure EBM into this space. The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. Evidence-based clinical practice requires integration of individual clinical expertise and patient preferences with the best available external clinical evidence from systematic research and consideration of available resources. EBM can be considered a subcategory of evidence-based healthcare, which also includes other branches of health-care practice such as evidence-based nursing or evidence-based physiotherapy. EBM subcategories include evidence-based surgery and evidence-based cardiology (Guyatt et al. 2008, 783).     

The Professionalization of Science Studies: Cutting Some Slack

During the past hundred years or so, those scholars studying science have isolated themselves as much as possible from scientists as well as from workers in other disciplines who study science. The result of this effort is history of science, philosophy of science and sociology of science as separate disciplines. I argue in this paper that now is the time for these disciplinary boundaries to be lowered or at least made more permeable so that a unified discipline of Science Studies might emerge. I discuss representative problems that stand in the way of such an integration. These problems may seem so formidable in the abstract that no one in their right mind would waste their time trying to bring about a unified field of Science Studies. However, those of us who limit ourselves to the study of the biological sciences have already formed a society in which workers from all disciplines can share their expertise -- the International Society for the History, Philosophy and Social Studies of Science.     

Citation Analysis May Severely Underestimate the Impact of Clinical Research as Compared to Basic Research

Background

Citation analysis has become an important tool for research performance assessment in the medical sciences. However, different areas of medical research may have considerably different citation practices, even within the same medical field. Because of this, it is unclear to what extent citation-based bibliometric indicators allow for valid comparisons between research units active in different areas of medical research.

Methodology

A visualization methodology is introduced that reveals differences in citation practices between medical research areas. The methodology extracts terms from the titles and abstracts of a large collection of publications and uses these terms to visualize the structure of a medical field and to indicate how research areas within this field differ from each other in their average citation impact.

Results

Visualizations are provided for 32 medical fields, defined based on journal subject categories in the Web of Science database. The analysis focuses on three fields: Cardiac & cardiovascular systems, Clinical neurology, and Surgery. In each of these fields, there turn out to be large differences in citation practices between research areas. Low-impact research areas tend to focus on clinical intervention research, while high-impact research areas are often more oriented on basic and diagnostic research.

Conclusions

Popular bibliometric indicators, such as the h-index and the impact factor, do not correct for differences in citation practices between medical fields. These indicators therefore cannot be used to make accurate between-field comparisons. More sophisticated bibliometric indicators do correct for field differences but still fail to take into account within-field heterogeneity in citation practices. As a consequence, the citation impact of clinical intervention research may be substantially underestimated in comparison with basic and diagnostic research.     

Masking or blinding? An unscientific survey of mostly medical journal editors on the great debate

I intended to end the great debate about whether "masking" is preferred to "blinding" when describing clinical trials in which group assignment is concealed from patients, data collectors, and sometimes statisticians. I conducted a highly unscientific survey, mostly of medical journal editors from the World Association of Medical Editors, but also of several strangers and distant relatives. Respondents were asked whether they preferred masking, blinding, or had no preference or considered the distinction to be unimportant. More than 80 people responded, representing 6 continents and several languages. Masking was preferred to blinding 3 to 1. However, the number of people reporting that either term is acceptable or that the issue is unimportant was about the same as the number who voted for masking. I conclude that both terms are acceptable in the context of reporting clinical research and that either may be used without confusion. I pronounce the great debate dead.     

Evolutionary medicine: its scope, interest and potential

This review is aimed at readers seeking an introductory overview, teaching courses and interested in visionary ideas. It first describes the range of topics covered by evolutionary medicine, which include human genetic variation, mismatches to modernity, reproductive medicine, degenerative disease, host–pathogen interactions and insights from comparisons with other species. It then discusses priorities for translational research, basic research and health management. Its conclusions are that evolutionary thinking should not displace other approaches to medical science, such as molecular medicine and cell and developmental biology, but that evolutionary insights can combine with and complement established approaches to reduce suffering and save lives. Because we are on the cusp of so much new research and innovative insights, it is hard to estimate how much impact evolutionary thinking will have on medicine, but it is already clear that its potential is enormous.     

The Ishikawa cells from birth to the present

More than 20 years have passed since the Ishikawa cell line, a well-differentiated human endometrial adenocarcinoma cell line, was established. Because this cell line bears estrogen and progesterone receptors, the cells have been used in numerous basic research areas such as reproductive biology and molecular science, and has been distributed to more than a hundred institutes. However, even the Ishikawa cells, after long-term culture, tend to transform into undifferentiated cells. In addition, it has been reported that estrogen and progesterone receptors disappeared from the cells that I distributed. I therefore attempted to establish well-differentiated cells from the parent Ishikawa cells and to produce a new and good quality supply of this cell line. I believe that it is very important for the investigator who established a cell line to be responsible for maintaining the quality of the cells. That is why I have not deposited this cell line in any cell bank. I would like to take this opportunity to report the history of Ishikawa cells from establishment to the present.     

The success of science and social norms

In this paper I characterize science in terms of both invisible hand social organization and selection. These two processes are responsible for different features of science. Individuals working in isolation cannot produce much in the way of the warranted knowledge. Individual biases severely limit how much secure knowledge an individual can generate on his or her own. Individuals working in consort are required, but social groups can be organized in many different ways. The key feature of the social organization in science is that only working scientists can confer the most important reward in science--use--and scientists must use each other's work in order to succeed in realizing this goal. An analysis of science as a selection process serves quite a different function. Individual scientists strive to come up with novel solutions to significant problems. The question then becomes how to be creative. From a selective perspective, science as a process involves the production of numerous alternatives and a selection among them. A single scientist solving an important problem makes science look very efficient. Treating science as a selection process casts it in a very different light. In this paper I combine an invisible hand mechanism with a selective perspective in order to explain why science is as successful as it is. I do not make recourse to evolutionary epistemology in any of its traditional senses.     

Reframing placebo in research and practice

The terms 'placebo' and 'placebo effects' cause confusion among patients, practitioners and scientists. This confusion results in both the adoption of practices that have no evidence of specificity yet considerable risk (such as surgery for low back pain) or the elimination of clinical practices proven to facilitate healing because they are not 'better than placebo' (such as acupuncture for low back pain). In this article, I discuss these issues and introduce the concept of optimal healing environment as a framework for disentangling what is useful from placebo research for adopting into clinical practice in a manner that is ethical and evidence-based.     

Coordinated, network-based research as a strategic component of science in Brazil

Scientific research plays a fundamental role in the health and development of any society, since all technological advances depend ultimately on scientific discovery and the generation of wealth is intricately dependent on technological advance. Due to their importance, science and technology generally occupy important places in the hierarchical structure of developed societies, and they receive considerable public and private investment. Publicly funded science is almost entirely devoted to discovery, and it is administered and structured in a very similar way throughout the world. Particularly in the biological sciences, this structure, which is very much centered on the individual scientist and his own hypothesis-based investigations, may not be the best suited for either discovery in the context of complex biological systems, or for the efficient advancement of fundamental knowledge into practical utility. The adoption of other organizational paradigms, which permit a more coordinated and interactive research structure, may provide important opportunities to accelerate the scientific process and further enhance its relevance and contribution to society. The key alternative is a structure that incorporates larger organizational units to tackle larger and more complex problems. One example of such a unit is the research network. Brazil has utilized such networks to great effect in genome sequencing projects, demonstrating their relevance to the Brazilian research community and opening the possibility of their wider utility in the future.     

Competing Conceptions of Animal Welfare and Their Ethical Implications for the Treatment of Non-Human Animals

Animal welfare has been conceptualized in such a way that the use of animals in science and for food seems justified. I argue that those who have done this have appropriated the concept of animal welfare, claiming to give a scientific account that is more objective than the “sentimental” account given by animal liberationists. This strategy seems to play a major role in supporting merely limited reform in the use of animals and seems to support the assumption that there are conditions under which animals may be raised and slaughtered for food that are ethically acceptable. Reformists do not need to make this assumption, but they tend to conceptualize animal welfare is such a way that death does not count as harmful to the interests of animals, nor prolonged life a benefit. In addition to this prudential value assumption, some members of this community have developed strategies for defending suitably reformed farming practices as ethical even granting that death and some other forms of constraints are harms. One such strategy is the fiction of a domestic contract. However, if one accepts the conceptualization of human welfare give by L. W. Sumner, and applies it to animals in the way that I think is justified, an accurate conceptualization of animal welfare has different implications for which uses of animals should be regarded as ethically acceptable. In this paper I give an historical and philosophical account of animal welfare conceptulization and use this account to argue that animal breeders, as custodians of the animals they breed, have the ethical responsibility to help their animal wards achieve as much autonomy as possible in choosing the form of life made available to them and to provide that life. Attempts to avoid these implications by alluding to a contract model of the relationship between custodians and their wards fail to relieve custodians of their ethical responsibilities of care.     

急诊医疗中医用粘合剂的研究进展

医用粘合剂是能够应用于医疗范畴的一类具有一定生物相容性和高度粘合力的医学材料;并已得到广泛的关注和研究。本文对当前急诊医疗中医用粘合剂的分类、各类粘合剂的作用机理、特点及应用范畴、医用粘合剂复合生物材料构成复合物的基础和应用研究现状等做一回顾及评价,并对未来医用粘合剂的研究和发展趋势进行了展望。     

Rethinking Reductionism,or, the Transformative Work of Making the Same

Plant-based drug discovery has long served as an iconic instance of both the power and the folly of scientific reductionism: this is a project, after all, that seeks to turn complex indigenous therapeutic practices into isolated molecules, to be scaled-up, and set into mass circulation. This arena has, for good reason, served as an example of the economic and epistemological violences enacted in forms of ‘recognition’ or ‘translation’ that treat scientific idioms and industrial value as the arbiters of truth and value. But here, I ask whether we are giving too much away, in analytic terms, when we take reductionism for granted. In this essay, I draw on my ethnographic research in Mexico, as well as broader philosophical debates, to suggest critical resources that might allow us to do something other than restage the familiar, infelicitous encounter between ‘embedded’, relational indigenous knowledges and isolating, abstracting, reductionist science. Here, I consider pharmaceutical research and development as a process that works less by reducing than by proliferating materials: in particular, by producing and recontextualising chemical compounds as simultaneously the same, and not the same. This formula has a strong place in pharmaceutical chemistry, and it resonates somewhat surprisingly in domains ranging from transnational drug regulation, to marketing strategies for generic drugs in Mexico, to debates within the philosophy of chemistry about the nature of chemical entities themselves. These conversations offer conceptual resources for rethinking reduction(ism), itself one of the key operators in charged projects of recognising and translating knowledge.