Collaboration to Understand Complex Diseases

The strategy of intellectual collaboration has accelerated modern research and research success. Identified by Professor Robert Adams in 2013 as the Fourth Age of Research collaboration is evident through ever increasing numbers of international multicenter publications. These tend to provide positive benefits in terms of citation; indeed Universities with a lower percentage of home grown papers have higher research incomes. The European Commission has placed collaboration at the heart of its research strategy and reported on the economic benefits. Emerging economies such as those of South America have also recognized the benefit of international collaboration. Much of the effort has been bottom up, that is, through researcher led collaborations, such as in the field of genetics, for example, genomics. Cancer, diabetes mellitus, and Alzheimer disease research have all benefited through extensive collaborative efforts. We have developed a consortium to emulate the best of this collaborative spirit, known as Global Pregnancy Collaboration (CoLab). CoLab, from its inception in 2010 has focused on adverse pregnancy outcomes and achieving a better understanding of their causes (online-only Data Supplement). Here, we review the pathologies we seek to understand and explain why better understanding mandates a global network of scientific and clinical experience. We present preeclampsia as a prototypical disorder but similar networks and collaboration are mandatory for understanding all human disease and, in particular, rare disorders. We highlight some of the challenges to collaborative studies, despite the overarching view, with supporting evidence, that this approach benefits all, and is to be encouraged. These challenges are not isolated to our discipline. We seek to bring attention to common hindrances, drawn from experiences within the CoLab consortium and suggest possible solutions. Preeclampsia: Potential for Gain From Collaboration Adverse pregnancy outcomes such as preeclampsia, preterm labor, stillbirth, and fetal growth restriction continue to be major causes of morbidity and mortality for mothers and infants, particularly in lowand middle-income countries (LMIC). In high-income countries (HIC), empirical strategies have been moderately successful in palliating some aspects of morbidity, but even in HIC these conditions continue to plague pregnant women and their offspring. This, despite the fact, that technological and academic advances in bioscience have greatly increased our understanding of the pathophysiology of these disorders. In a recent article focused on preeclampsia, we asked the question, “If we know so much about preeclampsia, why haven’t we cured the disease?” Preeclampsia provides a typical example of a disorder in which research confined to small-scale studies, and geographical location has hindered successful understanding and progress toward treatment or cure. Over 2000 years ago, it was recognized that seizures that abated with delivery occurred in some pregnant women. This disorder, eclampsia was, until the beginning of the 20th century considered a pregnancyspecific seizure disorder. The discovery that these seizures were accompanied by the new onset of proteinuria, and elevated blood pressure led to the recognition that these signs preceded seizures (hence preeclampsia) and were associated with fetal and maternal death and morbidity, even without seizures. The first impediment to progress in preeclampsia research was the likely erroneous conclusion that these nonspecific criteria identified a single disorder. The clinical characteristics of preeclampsia are extraordinarily diverse. The syndrome presents sometimes as almost immediately life threatening, and at others as a slowly progressive disorder, usually occurring in the last few weeks of pregnancy but occasionally much earlier. Fetal growth restriction is also not a constant, occurring