Multiple endocrine neoplasias in the era of translational medicine.

Medicine is an ever changing art, continuously adjusting to the shifting principles of philosophy and constant discoveries of science; it was beautifully said by Hippocrates: "... medicine does not do the same thing at this moment and the next..." Unabated dissemination of information is the only way that patients are assured that physicians will continue to practice medicine that reflects contemporary science. In the field of Multiple Endocrine Neoplasias (MENs), this is at least in part accomplished by biennially held International Workshops. The articles led by this editorial are the second and last installment of a collection of state-of-the-art presentations given in the course of the ninth such workshop that was held in Bethesda, MD, June 19-22, 2004. In addition to serving as an introduction to the articles that were written by some of the leaders in the field, the text of the editorial review that follows also supports the notion that MENs are poised to lead translational research in endocrinology: these disorders have benefited remarkably from the discoveries of the human genome project and are at a unique position to take advantage of new modalities in basic and clinical science.     

The doctor and the "delta factor": Walker Percy and the dilemma of modern medicine

As medical science progresses, a tension has developed between the art of medicine, which deals with patients as individual persons, and the science itself, which focuses on the objective pathology.This tension is furthered as medicine identifies itself increasingly with science. To explore the consequences of this unbalanced identification, and the strain it places on the physician-patient relationship, this article examines the thought of Walker Percy, and in particular his novel The Second Coming. In this novel, Percy, a physician by training, presents a case of a patient suffering at the hands of medicine-turned-reductionist. The novel highlights the breakdown of communication between physician and patient within modern medicine, and raises important questions about how to best understand, and thereby preserve, medicine's true art.     

Epistemic causality and evidence-based medicine

Causal claims in biomedical contexts are ubiquitous albeit they are not always made explicit. This paper addresses the question of what causal claims mean in the context of disease. It is argued that in medical contexts causality ought to be interpreted according to the epistemic theory. The epistemic theory offers an alternative to traditional accounts that cash out causation either in terms of "difference-making" relations or in terms of mechanisms. According to the epistemic approach, causal claims tell us about which inferences (e.g., diagnoses and prognoses) are appropriate, rather than about the presence of some physical causal relation analogous to distance or gravitational attraction. It is shown that the epistemic theory has important consequences for medical practice, in particular with regard to evidence-based causal assessment.     

中西医观解读时间生物学

时间生物学是一门研究生命活动节律的科学。在西方医学中,研究时间生物学是利用分子生物学实验来阐释其机制,以西医的思维方法解释时间生物学的生理及病理过程;中医对时间生物学的记载有两千多年的历史,阴阳理论、子午流注学说以及五运六气学说一直以来都在指导中医的诊断和治疗。中西医观的不同对时间生物学的研究提供了新的研究思路,同时时间生物学也为研究中西医结合提供了广阔的前景。     

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.     

Forensic culture as epistemic culture: The sociology of forensic science

This paper explores whether we can interpret the notion of ‘forensic culture’ as something akin to what Knorr-Cetina called an ‘epistemic culture’. Can we speak of a ‘forensic culture’, and, if so, how is it similar to, or different from, other epistemic cultures that exist in what is conventionally called ‘science’? This question has important policy implications given the National Academy Science’s (NAS) recent identification of ‘culture’ as one of the problems at the root of what it identified as ‘serious deficiencies’ in U.S. forensic science and ‘scientific culture’ as an antidote to those problems. Finding the NAS’s characterisation of ‘scientific culture’ overly general and naïve, this paper offers a preliminary exploration of what might be called a ‘forensic culture’. Specifically, the paper explores the way in which few of the empirical findings accumulated by sociologists of science about research science seem to apply to forensic science. Instead, forensic science seems to have developed a distinct culture for which a sociological analysis will require new explanatory tools. Faithful sociological analysis of ‘forensic culture’ will be a necessary prerequisite for the kind of culture change prescribed by external reformist bodies like the NAS.     

Evidence-based medicine,opinion-based medicine,and real-world medicine

The freedom of a doctor to treat an individual patient in the way he believes best has been markedly limited by the concept of evidence-based medicine. Clearly all would wish to practice according to the best available evidence, but it has become accepted that "evidence-based" means that which is derived from randomized, and preferably double-blind, clinical trials. The history of clinical trial development, which can be traced to the use of oranges and lemons for the treatment of scurvy in 1747, has reflected a progressive need to establish whether smaller and smaller effects of treatment are real. It has led to difficult concepts such as "equivalence" and aberrations such as "meta-analysis." An examination of evidence-based practice shows that it has usually been filtered through the opinions of experts and journal editors, and "opinion-based medicine" would be a more appropriate term. In the real world of individual patients with multiple diseases who are receiving a number of different drugs, the practice of evidence-based (or even opinion-based) medicine is extremely difficult. For each patient a judgment has to be made by the clinician of the likely balance of risks and benefits of any therapy. Good practice still requires clinical freedom for doctors.     

Science and craftsmanship: the art of experiment and instrument making

In his two-volume monograph Untersuchungen über thierische Elektricit?t, the Berlin physiologist Emil du Bois-Reymond described the relation between nervous electricity and muscle mechanics by way of a long series of experiments. This work is a key text in the history of the experimental life sciences. But it not only contains new findings about the functioning of muscles and its nerves. Du Bois-Reymond practiced an art of experimentation in which aesthetics of mechanical craftsmanship allied itself with the science of physiology. Experimentation, as du Bois-Reymond understood it, was simultaneously an epistemic and an aesthetic practice. The goal of his science was thus producing both knowledge and aesthetic success.     

Evidence-based medicine: watching out for its friends

An old joke states that one need not worry about one's enemies, but may be in danger from one's friends. We review a number of "enemies" and "friends" of evidence-based medicine (EBM). To understand where these enemies and friends have come from, it is important to see how the rise of EBM has created shifts in power, especially within academic medicine. Attacks from "enemies"-especially the criticism that EBM amounts to overturning a medicine of the individual in favor of an undesirable population medicine-tend to reflect misunderstandings of EBM, or of the degrees of uncertainty inherent in medicine itself, rather than substantive criticisms. The activities of three categories of so-called friends might well give EBM an undesirable reputation. These "friends" are the practitioners of a crude version of EBM (uncritical acceptance of randomized controlled trials while rejecting all other forms of evidence), commercial sponsors of clinical trials whose biases distort the available evidentiary base, and bureaucrats who employ EBM practices in the service of inequitable rationing of health resources.     

Technology and medicine

Technology, which is older than science, has been of vital importance in the development of modern medicine. Even so, there are voices of dissent to be heard. The disenchantment with technology expressed by Aldous Huxley in Brave new world has been echoed by contemporary writers on the technology of modern medicine. Medicine is seen by some to have been dehumanized by technology, and techniques that are expensive are thought to be consuming a greater proportion of health resources than they deserve. The practice of medicine has, nevertheless, been transformed by modern technology and diagnostic techniques and therapeutic measures undreamed of a few short decades ago are now commonplace. There is no reason why these developments should be any more dehumanizing than the use of similar techniques in modern transportation or communication, nor is their expense out of proportion when compared with other demands on the nation's purse. British workers have been at the forefront of many recent advances. Yet, even though the National Health Service provides a ready market for the products of British medical technology, the nation depends to an inordinate degree on imported products. In the development of appropriate medical technology there is an urgent need for better communication between inventors, scientists, industrialists and the National Health Service. At the same time there is an equal need for improved evaluation of untried techniques. The pressure for a central integrating body to coordinate resources could well be supported by the establishment of evaluation units in the different health authorities in this country.     

Beyond the surgeon's skill

The scientific attainments of medical science have advanced greatly in this generation. The art of the practice of medicine has not kept pace. The kindly spirit, unselfish service, and spiritual uplift which were characteristic of most physicians in the "horse-and-buggy days" are needed more today than they were a generation ago. A combination of medical science and spiritual counseling will do much to relieve the sufferings of mind and body. The personal physician-patient relationship and the building up of the patient's confidence in his physician are a most important aspect of the physician's duty. A belief in God and a knowledge of the availability of help from above is of great benefit to both physician and patient.     

The French are different. French and American medicine in the context of AIDS.

Medicine has often been approached as a thing apart from culture, as a uniform Western science. Within the past 10 years, we have begun to recognize that medicine is a system of beliefs and practices intrinsically linked to its larger sociocultural context. Still, it is generally perceived as uniform across North America and Western Europe. My recent research on French and American medical perspectives on the acquired immunodeficiency syndrome (AIDS) challenges this view by exploring differences in the structure of health care, the physician-patient relationship, and the conceptualizations of disease, particularly AIDS. These differences are not specific to AIDS, but the disease serves to exemplify them and to act as a medium for expressing what makes French and American medicine distinct. Global epidemics such as AIDS require both international response and cross-cultural understanding.     

Toward precision medicine of breast cancer

In this review, we report on breast cancer’s molecular features and on how high throughput technologies are helping in understanding the dynamics of tumorigenesis and cancer progression with the aim of developing precision medicine methods. We first address the current state of the art in breast cancer therapies and challenges in order to progress towards its cure. Then, we show how the interaction of high-throughput technologies with in silico modeling has led to set up useful inferences for promising strategies of target-specific therapies with low secondary effect incidence for patients. Finally, we discuss the challenge of pharmacogenetics in the clinical practice of cancer therapy. All these issues are explored within the context of precision medicine.     

Bioengineering considerations in liver regenerative medicine

Background

Liver disease contributes significantly to global disease burden and is associated with rising incidence and escalating costs. It is likely that innovative approaches, arising from the emerging field of liver regenerative medicine, will counter these trends.

Main body

Liver regenerative medicine is a rapidly expanding field based on a rich history of basic investigations into the nature of liver structure, physiology, development, regeneration, and function. With a bioengineering perspective, we discuss all major subfields within liver regenerative medicine, focusing on the history, seminal publications, recent progress within these fields, and commercialization efforts. The areas reviewed include fundamental aspects of liver transplantation, liver regeneration, primary hepatocyte cell culture, bioartificial liver, hepatocyte transplantation and liver cell therapies, mouse liver repopulation, adult liver stem cell/progenitor cells, pluripotent stem cells, hepatic microdevices, and decellularized liver grafts.

Conclusion

These studies highlight the creative directions of liver regenerative medicine, the collective efforts of scientists, engineers, and doctors, and the bright outlook for a wide range of approaches and applications which will impact patients with liver disease.

     

Philosophy of medicine is what philosophers of medicine do

Philosophy of medicine cannot be precisely defined because neither philosophy nor medicine can be precisely defined. Furthermore, philosophers of medicine do not constitute a well-defined class because they come not only from the fields of philosophy and medicine, but also from various other disciplines. Hence, I argue for a broad conception of philosophy of medicine that includes philosophical reflection on any matter considered to belong to medicine. A brief survey of the philosophy of medicine literature supports this view. Of the 625 articles surveyed for the years 1997-2006, nearly three-quarters dealt with matters of ethics, and of the 36 books surveyed, nearly 60% were primarily on ethics. Nonetheless, articles and books focusing on all other major branches of philosophy--metaphysics, epistemology, aesthetics, and logic--were also published. Moreover, many of the articles, even those primarily on ethics, dealt in significant ways with more than one branch of philosophy. I conclude that philosophy of medicine includes all sorts of philosophical reflection on medicine but is currently dominated by ethics. Given the stated purpose of journals and book series devoted to philosophy and medicine, this leaves ample room to expand other philosophical reflection on medicine.     

The role of basic science in evidence-based medicine

Proponents of Evidence-based medicine (EBM) do not provide a clear role for basic science in therapeutic decision making. Of what they do say about basic science, most of it is negative. Basic science resides on the lower tiers of EBM’s hierarchy of evidence. Therapeutic decisions, according to proponents of EBM, should be informed by evidence from randomised studies (and systematic reviews of randomised studies) rather than basic science. A framework of models explicates the links between the mechanisms of basic science, experimental inquiry, and observed data. Relying on the framework of models I show that basic science often plays a role not only in specifying experiments, but also analysing and interpreting the data that is provided. Further, and contradicting what is implied in EBM’s hierarchy of evidence, appeals to basic science are often required to apply clinical research to therapeutic questions.     

Emerging genomic technologies and the concept of personalized medicine: An overview of ethical,legal and social implications

With the completion of the Human Genome Project in May 2006, genetic testing for every American is rapidly becoming a reality. As the advanced technology fuels the path towards personalized medicine, genetic nondiscrimination legislation follows closely behind. It seems that the 2007 Genetic Information Nondiscrimination Act (GINA) will finally pass through both chambers of Congress and will be signed by the President, but questions remain. On May 1, 2008, the House passed GINA by a vote of 414 to 1. Why is this the year that genetic nondiscrimination legislation could finally become the reality? Is this the beginning of a new relationship between science and policy, where policy is finally catching up? We examine the answers to these questions through a look at the history of genetic nondiscrimination legislation and where it stands today, including arguments for and against the bill. We conclude by discussing how we can achieve a future of safe personalized medicine for the populous, which would require continuous productive interactions between policymakers and scientists.     

FDA and NIST collaboration on standards development activities supporting innovation and translation of regenerative medicine products

The development of standards for the field of regenerative medicine has been noted as a high priority by several road-mapping activities. Additionally, the U.S. Congress recognizes the importance of standards in the 21st Century Cure Act. Standards will help to accelerate and streamline cell and gene therapy product development, ensure the quality and consistency of processes and products, and facilitate their regulatory approval. Although there is general agreement for the need of additional standards for regenerative medicine products, a shared understanding of standards is required for real progress toward the development of standards to advance regenerative medicine. Here, we describe the roles of standards in regenerative medicine as well as the process for standards development and the interactions of different entities in the standards development process. Highlighted are recent coordinated efforts between the U.S. Food and Drug Administration and the National Institute of Standards and Technology to facilitate standards development and foster science that underpins standards development.