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"Falk, Raphael"
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Mutagenesis as a Genetic Research Strategy
Morgan's three students (Muller, Sturtevant, and Bridges) introduced reductionist empirical methods to the study of the chromosomal theory of heredity. Herman J. Muller concentrated on mutations, namely changes in the heterocatalytic properties of genes, without losing their autocatalytic (self-replication) properties. Experimental induction of mutations allowed quantitative analyses of genes' parameters, but hopes to deduce their chemicophysical character were never fulfilled. Once the model for DNA structure was proposed, the reductionist notions of mutation analysis were successfully applied to the molecular genes. However, it was soon realized that the concept of the particulate gene was inadequate. The more the molecular analysis of the genome advanced, the clearer it became that the entities of heredity must be conceived within systems' perspectives, for which special tools for handling large number of variables were developed. Analytic mutagenesis, however, continues to be a major strategy for the study of the cellular and chromosomal mechanisms that control mutation inductions.
Journal Article
The Relationship Between Geographic Variations and Overuse of Healthcare Services: A Systematic Review
Objective: To examine the relationship between overuse of healthcare services and geographic variations in medical care. Design: Systematic Review. Data Sources: Articles published in Medline between 1978, the year of publication of the first framework to measure quality, and January 1, 2009. Study Selection: Four investigators screened 114,830 titles and 2 investigators screened all selected abstracts and articles for possible inclusion and extracted all data. Data Extraction: We extracted data on rates of overuse in different geographic areas. We also extracted data on underuse, if available, for the same population in which overuse was measured. Results: Five papers examined the relationship between geographic variations and overuse of healthcare services. One study in 2008 compared the appropriateness of coronary angiography (CA) for acute myocardial infarction in high-cost areas versus low cost areas in the Medicare population and found largely similar rates of inappropriateness (12.2% vs. 16.2%). A study in 2000 using national data concluded that overuse of CA explained little of the geographic variations in the use of this procedure in the Medicare program. An older study of Medicare patients found similar rates of inappropriate use of CA (15% to 17% vs. 18%), endoscopy (15% vs. 18% 19%), and carotid endarterectomy (29% vs. 30%) in low-use and high-use regions. A small area reanalysis of data from this study of 3 procedures found no evidence of a relationship between inappropriate use of procedures and volume in 23 adjacent counties of California. Another 2008 study found that in-appropriate chemotherapy for stage I cancer was less common in low-cost areas compared with high-cost areas (3.1% vs. 6.3%). Conclusions: The limited available evidence does not lend support to the hypothesis that inappropriate use of procedures is a major source of geographic variations in intensity and/or costs of care. More research is needed to improve our understanding of the relationship between geographic variations and the quality of care.
Journal Article
Overuse and Systems of Care: A Systematic Review
Background: Current health care reform efforts are focused on reorganizing health care systems to reduce waste in the US health care system. Objective: To compare rates of overuse in different health care systems and examine whether certain systems of care or insurers have lower rates of overuse of health care services. Data Sources: Articles published in MEDLINE between 1978, the year of publication of the first framework to measure quality, and June 21, 2012. Study Selection: Included studies compared rates of overuse of procedures, diagnostic tests, or medications in at least 2 systems of care. Data Extraction: Four reviewers screened titles; 2 reviewers screened abstracts and full articles and extracted data. Results: We identified 7 studies which compared rates of overuse of 5 services across multiple different health care settings. National rates of inappropriate coronary angiography were similar in Medicare HMOs and Medicare FFS (13% vs. 13%, P = 0.33) and in a state-based study comparing 15 hospitals in New York and 4 hospitals in a Massachusetts-managed care plan (4% vs. 6%, P > 0.1). Rates of carotid endarterectomy in New York State were similar in Medicare HMOs and Medicare FFS plans (8.4% vs. 8.6%, P = 0.55) but non-recommended use of antibiotics for the treatment of upper respiratory infection was higher in a managed care organization than a FFS private plan (31% vs. 21%, P = 0.02). Rates of inappropriate myocardial perfusion imaging were similar in VA and private settings (22% vs. 16.6%, P = 0.24), but rates of inappropriate surveillance endoscopy in the management of gastric ulcers were higher in the VA compared with private settings (37.4% vs. 20.4%—23.3%, P < 0.0001). Conclusions: The available evidence is limited but there is no consistent evidence that any 1 system of care has been more effective at minimizing the overuse of health care services. More research is necessary to inform current health care reform efforts directed at reducing overuse.
Journal Article
The Forgotten Dispute: A.I. Oparin and H.J. Muller on the Origin of Life
The debate between A.I. Oparin's heterotrophic proposal of the origin of life and H.J. Muller's suggestion that what may be considered a posteriori the beginning of life, was an autocatalytic, replicative gene, is analyzed. Although both recognized that what was needed was an interacting system contiguous in space and time, it is now rarely mentioned that this scientific confrontation went on for several decades against the background of intense ideological issues, political tensions, and scientific developments that include the rise and demise of Lysenkoism, on the one hand, and, on the other, the establishment of neoDarwinism and the birth of molecular biology. Whereas for Oparin life was the outcome of the step-wise slow process of precellular evolution in which membrane-bounded polymolecular systems played a key role, Muller argued that life started with the appearance of the first nucleic-acid (DNA) molecule in the primitive oceans. Oparin and Muller came from different scientific backgrounds and almost opposite intellectual traditions, so their common interest in the origin of life did nothing to assuage their opposing views, which as argued soon became part of the debates that took place within the framework of intense ideological confrontations.
Journal Article
The Recent Evolution of the Question \What is Life?\
The question \"What is life?\" is absent from the writings of present-day biologists and scientists. However, an answer to this question, even if only partial, is needed for successful completion of projects in astrobiology and synthetic biology. The reasons for this absence are metaphysical, epistemological, and historical. No one has a full answer to this question, but there are many good reasons to keep posing it. Answers are no longer sought in the existence of strengths or mechanisms specific to life. The secret of life has been unveiled and it is nothing other than physical chemistry. What remains to be understood is the way the characteristics of organisms have emerged and been combined within one unique \"object.\" The answer to the question \"What is life?\" is now looked for in the scenario that generated life.
Journal Article
Mendel's Impact
Argument I wish to propose that the history of genetics reflects the history of the concept of reductionism in the life sciences. Reductionism is the thesis that explanation of laws or phenomena in one realm by those of another realm are always likely to be successful as explanations. By 1900 reduction of biology to the laws of chemistry and physics was not self evident: Although bottom-up preformationist explanations were largely inadequate for development, top-down epigenetic hypotheses often adopted metaphysical assumptions. Similarly, top-down theories of evolution as dependent on the accumulated impact of the past confronted those of bottom-up notions of fitness of specific traits that are relevant for future evolution. Mendel's 1865 methodological reductionist study of inheritance of traits was embraced in 1900 as evidence for reduction at the conceptual level. With the achievements of research of the mechanisms of inheritance, genetics became increasingly genocentric in its explanatory arsenal of development, and accordingly it was in conflict with the top-down, life-as-organized-systems' notions of embryology. Similarly, evolution was conceptually reduced to changes of gene-frequencies in populations. It was, however, precisely the increasing attempts to ground the bottom-up approach at the molecular level that eventually pushed conceptual reductionism to its crisis. Modern developments of molecular and computational methods finally forced, or allowed, researchers to apply bottom-up methodologies to top-down systems' analyses.
Journal Article