Genomic research delivering on promises: From rejuvenation to vaccines and pharmacogenetics.

WHAT IS KNOWN AND OBJECTIVE: There has been astounding progress made in the treatment of disease over recent years. This progress is particularly marked in cell therapy and in the personalization of therapy based on genetic insight, an approach known as genomic medicine. Our objective is to comment on the progress made in cell and genomic medicine against an historical backcloth of the search for rejuvenation. COMMENT: In 1741, close to seven decades after Antoine van Leeuwenhoek first saw his microscopic animalcules, Abraham Trembley, a tutor in Leiden, reported on an organism that could regenerate itself. The strange organism was thought to hold the secret of life. If it does, we have yet to prise the secret out. However, the ensuing study of cell programming and induced stem cells has shed considerable light on cellular development and provided new insights on the rejuvenative capacity of organisms. Inventive scientists have provided a deeper understanding of cell replication and, from this, developed new medicines for an increasing range of diseases. Targeted therapies, oligonucleotide therapy, therapeutic monoclonal antibodies and pharmacogenetics are all new therapeutic areas originating from the improved insights. More will surely follow. WHAT IS NEW AND CONCLUSION: Immortality is for the gods, but man's search for its elusive secrets, perhaps as old as man himself, will continue. Huge leaps have been made, and effective medicines have been developed from our improved insights into the mechanism of life. However, only the foolish will predict how far this new knowledge will lead us, and more particularly, at what speed new therapies will follow.

From the Origins of Pharmacogenetics to First Applications in Psychiatry.

Pharmacogenetics is the division of science addressing how genetic factors contribute to the metabolism, response, and side effects of a given medication. What was once regarded as a subdivision of genetics and pharmacology is now recognized as its own field and has its own unique story of origin. While the term "pharmacogenetics" was coined by Friedrich Vogel in 1959, the relevance of inherited genetic traits in affecting the clinical outcome to xenobiotics has been observed long before. In fact, there is much hope that pharmacogenetics can help unravel the "mysteries" as to why different people may display variable responses to the same medication as well as identify new drug targets. This article will highlight the conceptual framework for pharmacogenetics advanced by pioneer scientists Arno Motulsky and Friedrich Vogel (both human geneticists), as well as Werner Kalow (clinical pharmacologist), leading up to the creation of modern pharmacogenetics. Finally, the practical implications and first steps toward implementation for current psychiatric treatment are reviewed followed by an outlook on future studies.

The First 50 Years of Molecular Pharmacology.

In this Perspective, former and current editors of Molecular Pharmacology, together with the guest editors for this 50th Anniversary Issue, provide a historical overview of the journal since its founding in 1965. The substantial impact that Molecular Pharmacology has had on the field of pharmacology as well as on biomedical science is discussed, as is the broad scope of the journal. The authors conclude that, true to the original goals for the journal, Molecular Pharmacology today remains an outstanding venue for work that provides a mechanistic understanding of drugs, molecular probes, and their biologic targets.

The promise of psychiatric pharmacogenomics.

Clinicians already face "personalized" medicine every day while experiencing the great variation in toxicities and drug efficacy among individual patients. Pharmacogenetics studies are the platform for discovering the DNA determinants of variability in drug response and tolerability. Research now focuses on the genome after its beginning with analyses of single genes. Therapeutic outcomes from several psychotropic drugs have been weakly linked to specific genetic variants without independent replication. Drug side effects show stronger associations to genetic variants, including human leukocyte antigen loci with carbamazepine-induced dermatologic outcome and MC4R with atypical antipsychotic weight gain. Clinical implementation has proven challenging, with barriers including a lack of replicable prospective evidence for clinical utility required for altering medical care. More recent studies show promising approaches for reducing these barriers to routine incorporation of pharmacogenetics data into clinical care.

Pharmacogenomics: history, barriers, and regulatory solutions.

Pharmacogenomics is the branch of pharmacology which looks at the influence of genetic variation on drug response, connecting particular genetic markers with the effectiveness or safety of a drug. Pharmacogenomic products promise to improve medical treatment, lower health care costs, and make the new drug pipeline for FDA approval more efficient. In the last fifteen years, the FDA has approved pharmacogenomic drugs to treat a variety of cancers, HIV-AIDS, and coronary artery disease. Yet, progress in the field of pharmacogenomics has lagged behind the optimistic predictions of many researchers and policymakers. A lack of clear regulatory guidance dealing with pharmacogenomic products has been a major barrier to progress in the field. The FDA has, however, made some headway. In a series of guidance documents released between 2005 and 2011, the FDA has clarified much of its policy with respect to the development, approval, and labeling of pharmacogenomic products. Despite these efforts, many regulatory questions remain unanswered. This paper highlights a number of these regulatory gaps and provides recommendations to address them in a way which encourages increased development and clinical uptake of pharmacogenomic products.

Farmacogenómica y farmacogenética, una visión molecular para la individualidad morbosa y medicamentosa / Pharmacogenomics and pharmacogenetics, molecular vision for drug morbosa and individuality

El conocimiento basado en la individualidad ha logrado la curación permanente de los pacientes que han elegido tratar sus padecimientos con el sistema homeopático. El doctor Samuel Federico Hahnemann describió el principio de la individualidad como parte fundamental del correcto ejercicio de la terapéutica homeopática. Por muchos años la medicina alopática ignoró a la individualidad, proponiendo que un fármaco actuaría de la misma forma en todos los pacientes. Actualmente, gracias a la biomedicina molecular ha surgido la farmacogenética, área que estudia la respuesta farmacológica del individuo de acuerdo con su genotipo. Su objetivo es optimizar el tratamiento a nivel individual y transitar hacia una terapia personalizada más segura y eficiente que permita al clínico seleccionar el fármaco correcto, así como la dosis adecuada para el paciente indicado. Los avances de la farmacogenética y la farmacogenómica son, sin lugar a dudas, avances en el soporte científico de la Homeopatía.

The homeopathic knowledge based on individuality, has achieved permanent cure for patients who have chosen to treat their ailments with it. Dr. Samuel Frederick Hahnemann described the principle of Individuality as a fundamental principle of Homeopathic Therapeutics practice. For many years allopathic medicine ignored individuality holding that a drug would act in the same way in all patients. Today, thanks to Molecular Biomedicine, Pharmacogenetics has emerged, thus studying the pharmacological response of the individual based on genotype. It aims to optimize individual treatment, goes to a personalized therapy safer and more efficient to allow clinicians to select the proper drug, at the adequate dose, for the right patient. Advances in Pharmacogenetics and Pharmacogenomics are undoubtedly, advances in scientific support of Homeopathy.

Farmacogenómica y farmacogenética, una visión molecular para la individualidad morbosa y medicamentosa / Pharmacogenomics and pharmacogenetics, molecular vision for drug morbosa and individuality

El conocimiento basado en la individualidad ha logrado la curación permanente de los pacientes que han elegido tratar sus padecimientos con el sistema homeopático. El doctor Samuel Federico Hahnemann describió el principio de la individualidad como parte fundamental del correcto ejercicio de la terapéutica homeopática. Por muchos años la medicina alopática ignoró a la individualidad, proponiendo que un fármaco actuaría de la misma forma en todos los pacientes. Actualmente, gracias a la biomedicina molecular ha surgido la farmacogenética, área que estudia la respuesta farmacológica del individuo de acuerdo con su genotipo. Su objetivo es optimizar el tratamiento a nivel individual y transitar hacia una terapia personalizada más segura y eficiente que permita al clínico seleccionar el fármaco correcto, así como la dosis adecuada para el paciente indicado. Los avances de la farmacogenética y la farmacogenómica son, sin lugar a dudas, avances en el soporte científico de la Homeopatía. (AU)

The homeopathic knowledge based on individuality, has achieved permanent cure for patients who have chosen to treat their ailments with it. Dr. Samuel Frederick Hahnemann described the principle of Individuality as a fundamental principle of Homeopathic Therapeutics practice. For many years allopathic medicine ignored individuality holding that a drug would act in the same way in all patients. Today, thanks to Molecular Biomedicine, Pharmacogenetics has emerged, thus studying the pharmacological response of the individual based on genotype. It aims to optimize individual treatment, goes to a personalized therapy safer and more efficient to allow clinicians to select the proper drug, at the adequate dose, for the right patient. Advances in Pharmacogenetics and Pharmacogenomics are undoubtedly, advances in scientific support of Homeopathy. (AU)

Bernard Lerer: recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine (Pacific Rim Association for Clinical Pharmacogenetics).

This article announces the recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine by the Pacific Rim Association for Clinical Pharmacogenetics (PRACP): Bernard Lerer, professor of psychiatry and director of the Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. The Werner Kalow Responsible Innovation Prize is given to an exceptional interdisciplinary scholar who has made highly innovative and enduring contributions to global omics science and personalized medicine, with both vertical and horizontal (transdisciplinary) impacts. The prize is established in memory of a beloved colleague, mentor, and friend, the late Professor Werner Kalow, who cultivated the idea and practice of pharmacogenetics in modern therapeutics commencing in the 1950s. PRACP, the prize's sponsor, is one of the longest standing learned societies in the Asia-Pacific region, and was founded by Kalow and colleagues more than two decades ago in the then-emerging field of pharmacogenetics. In announcing this inaugural prize and its winner, we seek to highlight the works of prize winner, Professor Lerer. Additionally, we contextualize the significance of the prize by recalling the life and works of Professor Kalow and providing a brief socio-technical history of the rise of pharmacogenetics and personalized medicine as a veritable form of 21(st) century scientific practice. The article also fills a void in previous social science analyses of pharmacogenetics, by bringing to the fore the works of Kalow from 1995 to 2008, when he presciently noted the rise of yet another field of postgenomics inquiry--pharmacoepigenetics--that railed against genetic determinism and underscored the temporal and spatial plasticity of genetic components of drug response, with invention of the repeated drug administration (RDA) method that estimates the dynamic heritabilities of drug response. The prize goes a long way to cultivate transgenerational capacity and broader cognizance of the concept and practice of responsible innovation as an important criterion of 21(st) century omics science and personalized medicine. A new call is presently in place for the 2016 PRACP Werner Kalow prize. Nominations can be made in support of an exceptional individual interdisciplinary scholar, or alternatively, an entire research team, from any region in the world with a record of highly innovative contributions to global omics science and/or personalized medicine, in the spirit of responsible innovation. The application process is straightforward, requiring a signed, 1500-word nomination letter (by the applicant or sponsor) submitted not later than May 31, 2015.

Pharmacogenetics at 50: genomic personalization comes of age.

The study of the genetics of drug responses has a long history but has provided only a few examples of gene variants that are relevant clinically. Here, we discuss the current state of the pharmacogenomics field with emphasis on the potential of data generated through drug development in order to shed new light on genetic variants predictive of therapeutic outcomes-and likewise the potential of pharmacogenomics to improve clinical trial design. We note some examples in which data from clinical trials have already provided clear pharmacogenomic insights and suggest ways in which genomic technology might be used successfully in drug development.

Genes and schizophrenia: from a Festschrift Seminar honoring William T. Carpenter Jr, MD.

Recent data have begun to elucidate the genetic architecture of schizophrenia, as well as provide new insights into the relationships of specific genetic factors across diagnostic boundaries, with specific symptom domains, and in the prediction of antipsychotic treatment response. Not surprisingly, work conducted at the Maryland Psychiatric Research Center (MPRC), led by Dr William Carpenter, has helped to guide the thinking behind much of this work, as well as contributed valuable data toward these efforts. In this article, I will briefly summarize some of the major findings emerging from these lines of research and highlight the role of the Dr Carpenter and his colleagues at the MPRC in this area.

How personalized medicine became genetic, and racial: Werner Kalow and the formations of pharmacogenetics.

Physicians have long puzzled over a well-known phenomenon: different patients respond differently to the same treatment. Although many explanations exist, pharmacogenetics has now captured the medical imagination. While this might seem part of the broader interest in all things genetic, the early history of pharmacogenetics reveals the specific factors that contributed to the emergence of genetics within pharmacology. This paper examines the work of one pioneering pharmacologist, Werner Kalow, to trace the evolving intellectual formations of pharmacogenetics and, in particular, the focus on race. Working in the 1950s and 1960s, Kalow made three arguments to demonstrate the relevance of genetics to pharmacology, based on laboratory techniques, analogies to differences between other animal species, and appeals to the logic of natural selection. After contributing to the emergence of the field, Kalow maintained his advocacy for pharmacogenetics for four decades, collecting more evidence for its relevance, navigating controversies about race and science, and balancing genetics against other possible explanations of patient variability. Kalow's work demonstrates the deep roots of the genetic and racial preoccupations in pharmacology. Understanding this history can restore attention to other explanations of individuality in medical practice, something of increasing importance given the current interest in personalized medicine.

Pharmacogenetics and anaesthesia: the value of genetic profiling.

Approximately 50 years ago, pharmacogenetics was described as a new field of medicine that may explain human drug action. Anaesthesia played a key role in the early investigations. An understanding of how a person's DNA influences drug metabolism and effectiveness may allow individually tailored prescriptions, improving outcomes and safety. The ultimate goal of pharmacogenetic research is to offer tailored personalised medicine to improve both the efficacy of medication and patient safety by helping to predict risk of adverse outcomes. In this review, we present a selection of historical landmarks where anaesthesia has been a catalyst for pharmacogenetic development. We examine the level of evidence and cite examples of candidate genes and common polymorphisms known to alter the response to peri-operative medication. Finally, we set forth current views and potential exciting perspectives that may arise from the application of pharmacogenetics to the daily practice of anaesthesia and pain medicine.

Pharmacogenetics in heart failure: how it will shape the future.

Pharmacogenomics is a growing field of research that focuses on how an individual's genetic background influences his or her response to therapy with a drug or device. Increasing evidence from clinical trials in patients with heart failure (HF) due to systolic dysfunction suggests that genetic variations can predict the occurrence of HF, influence the effects of standard therapies, and influence outcomes of HF patients. This article reviews the underlying principles of pharmacogenomics, discusses some of the complex variables that influence the investigational approach to pharmacogenomics, demonstrates how variations in genes encoding a variety of different proteins can influence the effects of pharmacologic agents, and describes the potential impact of pharmacogenomics on the treatment of patients with HF.