High-Priced Sickle Cell Gene Therapies Threaten to Exacerbate US Health Disparities and Establish New Pricing Precedents for Molecular Medicine.

Gene therapies to treat sickle cell disease are in development and are expected to have high costs. The large eligible population size - by far, the largest for a gene therapy - poses daunting budget challenges and threatens to exacerbate health disparities for Black patients, who make up the vast majority of American sickle cell patients.

Medical knowledge integration and "systems medicine": Needs, ambitions, limitations and options.

Medicine today is an extremely heterogeneous field of knowledge, based on clinical observations and action knowledge and on data from the biological, behavioral and social sciences. We hypothesize at first that medicine suffers from a disciplinary hyper-diversity compared to the level of conceptual interdisciplinary integration. With the claim to "understand" and cure diseases, currently with the label "Systems Medicine" new forms of molecular medicine promise a general new bottom-up directed precise, personalized, predictive, preventive, translational, participatory, etc. medicine. Our second hypothesis rejects this claim because of conceptual, methodological and theoretical weaknesses. In contrary, this is our third hypothesis; we suggest that top-down organismic systems medicine, related to general system theory, opens better options for an integrative scientific understanding of processes of health and disease.

Historical perspectives on the impact of n-3 and n-6 nutrients on health.

Current public advice from the Food and Nutrition Board (FNB) about essential fatty acids (EFA) has limited quantitative details about three processes: (1) similar dynamics for n-3 linolenic and n-6 linoleic polyunsaturated fatty acids (PUFA) in maintaining 20- and 22-carbon n-3 and n-6 highly unsaturated fatty acids (HUFA) in tissues; (2) different dynamics for tissue n-3 and n-6 HUFA during formation and action of hormone-like eicosanoids; (3) simultaneous formation of non-esterified fatty acids (NEFA) and low density lipoprotein (LDL) from very low density lipoprotein (VLDL) formed from excess food energy and secreted by the liver. This report reviews evidence that public health may benefit from advice to eat less n-6 nutrients, more n-3 nutrients and fewer calories per meal. Explicit data for linoleic acid fit an Estimated Average Requirement (EAR) near 0.1 percent of daily food energy (en%) meeting needs of half the individuals in a group, a Recommended Dietary Allowance (RDA) near 0.5 en% meeting needs of 97-98 percent of individuals, and a Tolerable Upper Intake Level (UL) near 2 en% having no likely risk of adverse health effects. Quantitative tools help design and monitor explicit interventions that could beneficially replace imprecise advice on "healthy foods" with explicit preventive nutrition.

New molecular biologist perspective and insight: DNA topoisomerases production by recombinant DNA technology for medical laboratory application and pharmaceutical industry

DNA topoisomerases are essential enzymes that control the topological state of DNA replication during mitosis. These enzymes are classified based on their mechanisms and physical properties. During mitosis, superhelical DNA must be unwound or relaxed by DNA topoisomerases prior to a decoding step by DNA processing enzymes, such as DNA polymerase and RNA polymerase. By blocking the reaction of resealing the breaks in the DNA ultimately can result in cellular death. Compounds that inhibit the catalytic function of these enzymes can serve as potential anticancer agents. DNA topoisomerases are found in nature and used as high quality and well-validated targets for the screening of potential anticancer agents. Our current work focuses on determining potential anticancer agents from natural resources using DNA topoisomerases as the screening targets. Large scale production of these enzymes using recombinant DNA technology in our academic laboratory is utilised to avoid dependence on expensive commercially available enzymes. The in-house produced enzymes can also be used to enhance our research in the field of molecular medicine by providing an enzyme source that can be used to screen potential anticancer agents, and for other newly developed diagnostic and medical research projects in the near future as well as a step in moving our efforts into the industrial sector.

Biospecimens, biomarkers, and burgeoning data: the imperative for more rigorous research standards.

Knowledge of the altered molecular landscapes in disease offers great promise for developing biomarker-based tests to improve diagnosis and optimize treatment. Progress in biomarker research has been frustratingly slow due to the poor clinical trial design and the lack of standards for specimen collection, biomarker analysis, and data reporting. The ability of high throughput genomics, proteomics, and other 'omics' platforms to profile a large number of analytes in a single assay, together with the pending prospect of rapid expansion of whole exome and whole genome sequencing for clinical use, is increasing the technical and logistical complexity of biomarker validation. Harnessing these new technologies and improved productivity in biomarker validation will depend on adopting systems-based approaches and require major changes in the organization and funding strategies for biomarker research. A systems approach will require new multi-institution collaborations, the integration of diverse technical and clinical activities, greater engagement of industry, and education of regulators, clinicians, and payers about how to use biomarkers for improved patient management and clinical outcomes.

Clinical requests for molecular tests: the 3-step evidence check.

Laboratory tests performed by molecular methods are increasing in volume and complexity at an unprecedented rate. Molecular tests have a broad set of applications, and most recently have been advocated as the mechanism by which providers can further tailor treatments to the individual patient. As the momentum behind molecular testing continues to increase, pathology practices may find themselves unprepared for the new wave of molecular medicine. This special article has been developed in an effort to provide pathologists who have limited molecular training with a simple and quick algorithm for determining whether a requested molecular test is appropriate for a patient. Additional recommendations for a more intensive and proactive review and management of molecular requests also are included. The principles discussed can easily be applied to requests for any test, including those not using molecular methods, which would be sent to an outside reference laboratory. This special article was developed from a Webinar for the College of American Pathologists targeting education for pathologists about the transformation of pathology practice in the new molecular and digital age.