Pain, paradox, and value

The author argues that "as soon as one begins to study the understanding and management of pain in science, human medicine, and veterinary medicine, one begins to encounter a variety of apparent paradoxes." He contends that these paradoxes, ten of which he identifies and discusses in this essay, are based on flawed philosophical and valuational assumptions underlying science and medicine. Rollins concludes that, as social morality increasingly has an impact on science, a new ideology will evolve that is more receptive to the moral universe and more capable of a "coherent vision of pain, one which acknowledges that the medical notion of adequacy of anaesthesia is as much a moral as a scientific one."     

Identification of a subversive substrate of Trichomonas vaginalis purine nucleoside phosphorylase and the crystal structure of the enzyme-substrate complex

Trichomonas vaginalis is an anaerobic protozoan parasite that causes trichomoniasis, a common sexually transmitted disease with worldwide impact. One of the pivotal enzymes in its purine salvage pathway, purine nucleoside phosphorylase (PNP), shows physical properties and substrate specificities similar to those of the high molecular mass bacterial PNPs but differing from those of human PNP. While carrying out studies to identify inhibitors of T. vaginalis PNP (TvPNP), we discovered that the nontoxic nucleoside analogue 2-fluoro-2'-deoxyadenosine (F-dAdo) is a "subversive substrate." Phosphorolysis by TvPNP of F-dAdo, which is not a substrate for human PNP, releases highly cytotoxic 2-fluoroadenine (F-Ade). In vitro studies showed that both F-dAdo and F-Ade exert strong inhibition of T. vaginalis growth with estimated IC(50) values of 106 and 84 nm, respectively, suggesting that F-dAdo might be useful as a potential chemotherapeutic agent against T. vaginalis. To understand the basis of TvPNP specificity, the structures of TvPNP complexed with F-dAdo, 2-fluoroadenosine, formycin A, adenosine, inosine, or 2'-deoxyinosine were determined by x-ray crystallography with resolutions ranging from 2.4 to 2.9 A. These studies showed that the quaternary structure, monomer fold, and active site are similar to those of Escherichia coli PNP. The principal active site difference is at Thr-156, which is alanine in E. coli PNP. In the complex of TvPNP with F-dAdo, Thr-156 causes the purine base to tilt and shift by 0.5 A as compared with the binding scheme of F-dAdo in E. coli PNP. The structures of the TvPNP complexes suggest opportunities for further improved subversive substrates beyond F-dAdo.     

Biohumanities: rethinking the relationship between biosciences, philosophy and history of science, and society

We argue that philosophical and historical research can constitute a "Biohumanities" that deepens our understanding of biology itself engages in constructive "science criticism," helps formulate new "visions of biology," and facilitates "critical science communication." We illustrate these ideas with two recent "experimental philosophy" studies of the concept of the gene and of the concept of innateness conducted by ourselves and collaborators. We conclude that the complex and often troubled relations between science and society are critical to both parties, and argue that the philosophy and history of science can help to make this relationship work.     

Scientific Imaginaries and Ethical Plateaus in Contemporary U.S. Toxicology

This article contributes to a growing literature in the anthropology of science, focusing on contemporary U.S. toxicology and the development of "toxicogenomics." Toxicogenomics research aims to understand impacts of environmental stressors at the genetic level and to create a "systems toxicology" that combines different kinds of biological data for holistic understanding. Toxicologists are challenged to deal with greater and greater complexity while fulfilling their historic mission of producing results relevant to regulatory, legal, and clinical decision making. Although there is now a robust body of anthropological work on the sciences—in practice, as sites of cultural production, and as cultural and political-economic forces in a variety of domains—a relatively underdeveloped theme is subject formation within the sciences. This article directs ethnographic attention toward understanding how scientific imaginaries take shape and interpolate technical, biomaterial, political-economic, social, cultural, and ethical elements. We map such efforts in contemporary toxicogenomics as an instance of "civic science."     

From "butyribacterium" to "E. coli": an essay on unity in biochemistry

New ideas in science frequently arise from neglected or distorted antecedents. This essay deals with the idea of biochemical unity, encapsulated in Jacques Monod's well-known phrase, dating from 1954: "Anything found to be true of E. coli must also be true of elephants." An earlier version of this phrase,--"From the elephant to butyric acid bacterium--it is all the same!"--was coined in 1926 by the Dutch microbiologist Albert Jan Kluyver. In that year Kluyver and his associate Hendrick Jean Louis Donker published a celebrated paper, "Unity in Biochemistry." The concept of biochemical unity had many antecedents, but these had never caught on. The Kluyver-Donker paper has often been regarded to provide a boost to biochemical and especially to microbiological thinking. Its interpretations and misinterpretations represent an encapsulated history of biochemistry. The present paper examines the history of the concept of biochemical unity from before to beyond Kluyver, investigates the two "elephant" phrases and their possible relationships, and ends with a discussion of the attractiveness of unifying ideas in science.     

Producing Absolute Truth: CSI Science as Wishful Thinking

ABSTRACT  Forensic science has come to be assigned an important role in contemporary crime fiction. In this article, I analyze the cultural repertoire of forensic science conveyed by the popular television show Crime Scene Investigation (CSI). I argue that CSI science, in delivering an absolute "truth" about how and by whom crimes have been committed, is equated with justice, effectively superseding nonfictional forensic science as well as nonfictional judicature as a whole. Thus, CSI as a cultural performance adds to the mediascape a repertoire of wishful-thinking science with which to think about perceptions of and desires for crime and justice in nonfictional society. This repertoire seems to be considered relevant enough to nonfictional society to cause concern about the judicial system, as expressed in discussions of the so-called " CSI effect."     

Epistemological reflections on the art of medicine and narrative medicine

This article challenges the widespread view that there is both a science and an art of medicine. Through examination of recent work in medical humanities --Jodi Halpern's From Detached Concern to Empathy (2001), Kathryn Montgomery's How Doctors Think (2006), and Rita Charon's Narrative Medicine (2006)--I argue that while a variety of epistemic techniques are important in medicine, it is not helpful to dichotomize them as "science" versus "art." I assess the epistemic strengths and weaknesses of narrative medicine, a recent exemplar of humanistic medicine.     

How to see the trees for the forest: introduction to a special issue on causation and disease

This paper summarizes the results from the first European Advanced Seminar in the Philosophy of the Life Sciences, which was held at the Brocher Foundation in Hermance (Switzerland) 6-10 September 2011. The Advanced Seminar brought together philosophers of the life sciences to discuss the topic of "Causation and Disease." The search for causes of disease in the biomedical sciences, we argue on the basis of the contributions to this conference, has not resulted in a simplification and unification of biomedical knowledge, as once hoped for by philosophers of science, but rather in its "complexification."     

Computational RNomics:Structure identification and functional prediction of non-coding RNAs in silico

The eukaryotic genome contains varying numbers of non-coding RNA(ncRNA) genes."Computational RNomics" takes a multidisciplinary approach,like information science,to resolve the structure and function of ncRNAs.Here,we review the main issues in "Computational RNomics" of data storage and management,ncRNA gene identification and characterization,ncRNA target identification and functional prediction,and we summarize the main methods and current content of "computational RNomics".     

When "personhood" begins in the embryo: avoiding a syllabus of errors

The following essay was delivered at the conference "Ontogeny and Human Life" at the Ponifical Athenaeum "Regina Apostolorum," November, 2007. Sponsored by the Legion of Christ, the Pontifical Academy for Life, and the John Templeton Foundation, the sessions focused on when the conceptus became a "person." My essay focused on the scientific conclusions that could aid such discussions. Moreover, after listening to the philosophical, legal, and theological discussions that ensued, I responded theologically as well. New concepts in modern embryology have made scientists revise their views concerning the autonomy of embryos and the mechanisms that generate such embryos. There are interactions between the sperm and the female reproductive tract and egg which had never been known until recently. There are also interactions between the developing organism and its environment that had been unsuspected a decade ago. Gut bacteria induce the development of the mammalian digestive system and immune system by changing the gene expression patterns in the mammalian intestine. Conversely, chemicals in our technological society can adversely affect the embryo, rendering it sterile or prone to tumors later in life. While there is no consensus among scientists as to when human life begins, both Church and science can become allies in persuading governments to regulate or ban the production and use of these fetotoxic chemicals. These new views of embryonic development change many of the stories told about human embryos and fetuses, and they have implications concerning the use of science as evidence for theological positions.     

Chance and serendipity in science: two examples from my own career

The usual scientific paper follows a rather narrowly (but not ever rigidly) defined pattern. Both the author and the journal like to see a linear logical presentation of a "story." Seldom does the paper give the reader the "backstory." Where did the idea come from in the first place? How many false leads led down blind alleys? What happened by chance and what by logical planning? Was there an element of serendipity involved? Perhaps as we enter the paperless era and do not have to count words quite so religiously, it may be possible to encourage a more freewheeling scientific paper, but for now, we have to rely on the historians of science and/or those who "tell all" about their own research. "Reflections" seems an appropriate space for the latter. I have chosen two scenarios from my own career in which happy accidents played important roles but, unhappily, received little recognition in my published papers.     

One hundred years of American botany: a short history of the Botanical Society of America

This paper offers highlights from the 100 (plus) years of the Botanical Society of America (BSA) and draws extensively on the archives of the BSA. In addition to examining the founding of the society and the attempt to "professionalize" botany in late 19th century America, the paper also explores the complex relations between the BSA and a number of related societies in the United States, the Society's struggle to create a coherent identity for itself, the place of botany as a whole in the context of the burgeoning biological sciences in the 20th century, and the changing role of the BSA in an international context. The paper assesses both the achievements and the challenges facing the BSA. It closes by offering some historical reflections on the status of "botany" as a science and the historical significance of terms like "plant biology" and "plant science."     

Terminology for contractions of muscles during shortening, while isometric, and during lengthening.

Communication among scientists must be clear and concise to avoid ambiguity and misinterpretations. The selection of words must be based on accepted definitions. The fields of biomechanics, muscle physiology, and exercise science have had a particularly difficult time with terminology, arising from the complexity of muscle contractions and by the use of inappropriate terminology by scientists. The dictionary definition of the verb "contract," specifically for the case of muscle, is "to undergo an increase in tension, or force, and become shorter." Under all circumstances, an activated muscle generates force, but an activated muscle generating force does not invariably shorten! During the 1920s and 1930s, investigators recognized that the interaction between the force generated by the muscle and the load on the muscle results in either shortening, no length change (isometric), or lengthening of the muscle. The recognition that muscles perform three different types of "contractions" required that contraction be redefined as "to undergo activation and generate force." Modifiers of contraction are then needed to clarify the lack of movement or the directionality of movement. Despite the contradiction, for 75 years the lack of movement has been termed an "isometric contraction." The directionality of the movement is then best described by the adjectives "shortening" and "lengthening." The definitions of "concentric" as "having the same center" and of "eccentric" as "not having the same center" are consistent with hypertrophy, or remodeling of the heart muscle, but are inappropriate to describe the contractions of skeletal muscles.     

Taking the Plunge: Next Steps in Engaged Learning: Project Kaleidoscope-Connecticut Conference of Independent Colleges Conference for Science Educators

College and university science educators from across Connecticut gathered at Yale's West Campus in April 2010 for a Project Kaleidoscope (PKAL) program entitled "Taking the Plunge: Next Steps in Engaged Learning." Funded by the National Science Foundation (NSF) and co-sponsored by the Connecticut Conference of Independent Colleges (CCIC) and Yale's McDougal Graduate Teaching Center, the event was the latest in a PKAL series of one-day conferences aimed at equipping science, technology, engineering, and math (STEM) instructors with effective approaches to engaging students and training future scientists.     

A Theoretical Foundation for Life-Cycle Assessment

The presence of value judgments in life-cycle impact assessment (LCIA) has been a constant source of controversy. According to a common interpretation, the international standard on LCIA requires that the assessment methods used in published comparisons be "value free." Epistemologists argue that even natural science rests on "constitutive" and "contextual" value judgments. The example of the equivalency potential for climate change, the global warming potential (GWP), demonstrates that any impact assessment method inevitably contains not only constitutive and contextual values, but also preference values. Hence, neither life-cycle assessment (LCA) as a whole nor any of its steps can be "value free." As a result, we suggest a more comprehensive definition of objectivity in LCA that allows arguments about values and their relationship to facts. We distinguish three types of truth claims: factual claims, which are based on natural science; normative claims, which refer to preference values; and relational claims, which address the proper relation between factual knowledge and values. Every assessment method, even the GWP, requires each type of claim. Rational arguments can be made about each type of claim. Factual truth claims can be assessed using the scientific method. Normative claims can be based on ethical arguments. The values of individuals or groups can be elicited using various social science methods. Relational claims must follow the rules of logic. Relational claims are most important for the development of impact assessment methods. Because LCAs are conducted to satisfy the need of decision makers to consider environmental impacts, relational claims about impact assessment methods should refer to this goal. This article introduces conditions that affect environmental decision making and discusses how LCA—values and all—can be defended as a rational response to the challenge of moving uncertain scientific information into the policy arena.     

ATTRIBUTES BELIEVED TO IMPACT FLAVOR: AN OPINION SURVEY

The definition of "flavor" is a term that appears to vary from one area to the next. A survey was conducted on 140 individuals in various areas of specialization (agriculture, food science, sensory evaluation, and the chemical senses) to see what sensations are thought to be involved in "flavor," as well as whether there were any differences in definitions across groups. The results demonstrate that while a fairly stable definition of the term does exist, there is some difference in what different groups of expertise mean when they refer to "flavor."     

Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function

Over 520 different amino acid substitution variants have been previously identified in the systematic screening of 91 human DNA repair genes for sequence variation. Two algorithms were employed to predict the impact of these amino acid substitutions on protein activity. Sorting Intolerant from Tolerant (SIFT) classified 226 of 508 variants (44%) as "Intolerant." Polymorphism Phenotyping (PolyPhen) classed 165 of 489 amino acid substitutions (34%) as "Probably or possibly damaging." Another 9-15% of the variants were classed as "Potentially intolerant or damaging." The results from the two algorithms are highly associated, with concordance in predicted impact observed for approximately 62% of the variants. Twenty-one to thirty-one percent of the variant proteins are predicted to exhibit reduced activity by both algorithms. These variants occur at slightly lower individual allele frequency than do the variants classified as "Tolerant" or "Benign." Both algorithms correctly predicted the impact of 26 functionally characterized amino acid substitutions in the APE1 protein on biochemical activity, with one exception. It is concluded that a substantial fraction of the missense variants observed in the general human population are functionally relevant. These variants are expected to be the molecular genetic and biochemical basis for the associations of reduced DNA repair capacity phenotypes with elevated cancer risk.     

Embryonic Induction

"Spemann's" lecture treats experiments on the separation ofthe first two cells of a frog, or sea urchin, or salamanderembryo; the induction of a lens in a frog embryo by an opticvesicle (primordium of the eye); and the primary organizer thatis a dynamic center, establishing the basic organization ofthe embryo and inducing the nervous system and sense organs."Spemann" goes beyond science in speaking poetically of thebeauty and order in the universe, and to illustrate how a goodscholar should work he uses a lovely metaphor of piecing togetherthe fragments of a broken vase. "Spemann" concludes with a stirringplea for academic freedom.     

Universal Human Rights and the Problem of Unbounded Cultural Meanings

Freedom from violence stands as an important candidate for a universal human right. By definition, however, such rights apply only to phenomena that are universally perceived and experienced and take predictable expression, a possibility that many contemporary interpretations of cultural theory reject. Yet people who live dramatically different lives—on tourist islands in the West Indies or as hunter-gatherers and reindeer herders in Arctic regions—agree about components that comprise a unitary phenomenon legitimately called "violence." This is consistent with findings from cognitive and neruological science and with a more Geertzian theory that culture understood as meaning is not a thing, cultural variability occurs between individuals, and cultural consensus emerges as a necessary consequence of social interaction among people who participate in common social fields, who engage in common social discourse.     

Welch, Sedgwick, and the Hopkins model of hygiene

William H. Welch and William T. Sedgwick, two of the founding fathers of American public health, were both early generation "Hopkins Men." Sedgwick was part of the first group of graduate students to attend Johns Hopkins University, and Welch was part of the initial faculty at the University's medical school. While they never worked together as colleagues at Hopkins, both became interested in the exciting new discoveries of the microbial nature of human disease and developed similar public health programs based on this information. Sedgwick expanded upon these investigations in the new sanitary science program at MIT, where academic public health first emerged in the United States following Sedgwick's appointment in 1883. Welch, who had been exposed to European research in microbiology, promoted microbial research in pathology in Baltimore in 1884. His laboratory-based investigations expanded until they led to the formation of the country's first school of public health in 1916. Thus, a "Hopkins Model" for hygiene and public health emerged from the efforts of both Welch and Sedgwick.