Precision Medicine 2.0: The Next Wave of Science

Next Generation Precision Medicine

Precision medicine and multiomics technologies that enable them (genomics, proteomics, and metabolomics) offer significant benefits to societies worldwide. These benefits can materialize, for example, through reductions in adverse drug reactions by systems diagnostics, promotion of healthy aging, precision nutrition and/or, socioeconomic benefits.

OMICS: A Journal of Integrative Biology has featured in September a special issue on the next wave of precision medicine science, termed as Precision Medicine 2.0. The October special issue expands upon the topic and deepens the discussion on Precision Medicine 2.0. The articles bring to the fore important topics that are previously understudied, underappreciated, or underfunded at the intersection of global and local precision medicine scholarship. We offer the following editorial highlights from the articles in the October special issue.

Mental health is important to functioning of individuals and welfare of societies. In 2010, 7.4% of the total global disease burden was attributable to mental and substance use disorders. This burden is anticipated to increase, particularly in low- and middle-income countries in the future. Dalvie et al. examine the salient findings from genome-wide association studies in the field of psychiatric pharmacogenomics, with a view to a global roadmap for precision medicine in psychiatry. Importantly, they note that the vast majority of pharmacogenomics work has thus far been undertaken in high-income countries on a relatively small proportion of the global population.

Sub-Saharan African countries suffer from a high prevalence of sickle cell disease, a genetic multisystem disorder associated with episodic pain and organ damage. In their comprehensive expert review, Mnika et al. report that there are only a limited number of studies that address the pharmacogenomics of analgesics and opioids in sickle cell disease. Equally important, they point to the problematic global distribution of studies from different geographical regions: no study has been conducted in sub-Saharan Africa where majority of the patients with this important and common disease reside. The authors conclude that sickle cell therapeutics is not yet ready for precision medicine, and alert the life sciences community for disparities in targeting of global research and innovation investments for sickle cell disease specifically, and precision medicine and pharmacology research broadly.

The introduction of highly active antiretroviral therapy in the 1990s has led to significant reductions in HIV-related deaths. Attention is turning to quality of life and long-term side effects for patients on life-long drug treatment. The World Health Organization is now ushering a new era in HIV prevention and treatment strategy at a commendable pace in Africa that has resulted in more than 16 million people receiving antiretroviral therapy by the end of 2015. In sub-Saharan Africa, efavirenz is the preferred first-line antiretroviral therapy. To this end, Masimirembwa et al. offer a broad contextual analysis on neuropsychiatric side effects of efavirenz, and the need for pharmacogenomics-guided pharmacovigilance (pharmacogenovigilance) as massive efavirenz-based roll out programs are being planned in the continent.

Geard et al. examine, in an expert review, the current data on epidemiology and genetic risk factors of stroke, pulmonary hypertension, and kidney disease associated with sickle cell disease. Stroke and kidney disease each affect ∼10% of patients, with pulmonary hypertension displaying a higher prevalence of 30% among adults with sickle cell disease. The authors note that these epidemiology figures may be an underestimate in patients living in Africa with sickle cell disease. Moreover, attesting, in part, to the mismatch, already noted, on global disease burden distribution and research investments, only a limited body of literature has identified the genetic factors that contribute to the risk for cardiovascular phenotypes in sickle cell disease. The authors call for socially responsible research investments through multi-omics research on cardiovascular outcomes associated with sickle cell disease, particularly in Africa, so as to allow for proportional investment of global research funding on diseases that greatly impact the African continent.

Alessandrini et al. focus on the prevention of adverse drug reactions, a central pillar of the current precision medicine initiatives worldwide. The authors discuss and emphasize the importance of the guidelines by the Clinical Pharmacogenetics Implementation Consortium, with a view to predicting and managing adverse drug reactions. In addition, they offer an expert analysis on the top 10 crosscutting opportunities and challenges facing the fields of precision medicine and pharmacogenomics, which have broad applicability independent of the drug class involved. The authors rightly note that many of these opportunities and challenges pertain to infrastructure, study design, policy, and science culture in the early 21st century.

Barlas et al. report on an important topic that has been virtually overlooked by the precision medicine community. Migrant, displaced, refugee populations, and their host communities require precision medicine and rational approaches to therapeutics as well. For example, in the aftermath of the Syrian civil war since 2011, millions have fled their homes to the neighboring countries in the eastern Mediterranean region. The authors explain that these social changes and population mobility demand faster regulatory decisions on pharmaceutical innovations. They propose a framework for “population-to-population bridging” of regulatory decisions, whereby novel drugs developed in or for particular regions/countries can meet with rational regulatory decisions/approval in world regions impacted by migrant/refugee populations. They report on four single nucleotide polymorphism variations in CYP2C9 and CYP2C19 genes from an eastern Mediterranean population that is currently hosting a vast number of migrant populations from Syria. Both CYP2C9 and CYP2C19 are very important pharmacogene (VIP) molecular targets.

The authors then compare the observed genetic variation in their sample with data on 12 world populations from the dbSNP and discuss the feasibility of forecasting the pharmacokinetics of drugs used by communities in the eastern Mediterranean region. In addition, they note the study has salience (1) for rational regulatory decision making through harnessing of VIP variation data in support of worldwide precision medicine and (2) as a catalyst to equitably support and invest in future research in migrant or refugee populations from Syria and elsewhere.

Judes et al. report, in a letter to the editors, new evidence on epigenetic heterogeneity within the triple negative breast cancer. A comprehensive epigenetic understanding of this breast cancer type is essential to develop innovative and effective drugs. Epigenetic biomarkers are at the epicenter of the next wave science agenda for precision medicine and deserve further research and clinical investments.

Concluding Remarks

The October special issue concludes our thematic focus on Precision Medicine 2.0. We welcome future peer-reviewed submissions and analyses to the Journal on this subject from different world regions and fields of application. Precision Medicine 2.0 dovetails on and supports the various programs for targeted therapeutics and systems diagnostics such as the U.S. Precision Medicine Initiative, a visionary and timely US$215-million program launched by President Obama in 2015.

As a Journal of Integrative Biology, the Journal offers a comprehensive and rigorously peer-reviewed knowledge platform in support of multidisciplinary innovation from cell to society. We have editorially emphasized, on many occasions, that scientific breakthroughs and knowledge-based innovation have multiple and complex social determinants, beyond design of and access to new technologies. Moving forward on Precision Medicine 2.0, OMICS will continue to champion high-quality peer-reviewed publications that address the gaps between science, technology, and global society, and life sciences and social sciences.

In the 21st century, we must not leap into assumptions about where precision medicine is most achievable or suitable. Indeed, striving to be nonassuming and inclusive at the intersection of global and local scholarship is one of the hallmarks of the Precision Medicine 2.0 notion that has been addressed in the two-part special issue in September and October. We trust you will enjoy reading these articles as much as we enjoyed editing them.