FROM CELLS TO SELVES Developmental Biology Understanding Normal and Abnormal Development Eunice Kennedy Shriver National Institute of Child Health and Human Development FROM CELLS TO SELVES Contents The NICHD Mission . 1 The Strategic Planning Process . 2 Introduction . 3 Scientific Goals of the Strategic Plan. 5 Genetic Studies of Birth Defects . 5 Basic Mechanisms of Normal and Abnormal Development . 6 Development of Model Systems . 8 Research Technologies and Resources. 10 Functional Genomics and Proteomics . 10 Imaging Technology and Visualization of Development Processes . 10 Developmental Databases . 11 Programs for the Study of the Developmental Biology of Birth Defects . 11 Training and Education . 12 Appendix—Roster of Advisors . 13 Developmental Biology: Understanding Normal and Abnormal Development i FROM CELLS TO SELVES The NICHD Mission The National Institute of Child Health and Human Programs at the NICHD are based on the concepts that Development (NICHD) seeks to ensure that every individual adult health and well-being are determined in large part is born healthy, is born wanted, and has the opportunity to by episodes early in life, sometimes before birth; that fulfill his or her potential for a productive life unhampered human development is continuous throughout life; and that by disease or disability. The Institute further strives to help optimal outcomes of development are important not only to parents have the children they want, at the times they want the individual but to society. NICHD research is also them, and to ensure that every mother experiences a directed toward restoring or maximizing individual pregnancy free of adverse complications. Key to the potential and functional capacity when disease, injury, or a success of this mission is answering the fundamental chronic disorder intervenes in the developmental process. questions of how a single fertilized cell eventually develops Thus, the NICHD mission truly spans the life cycle, and into a fully functional adult human being and how a much of the health and well-being of our population multitude of genetic and environmental factors influence depends on the success of the Institute’s research. that process for good or ill. Developmental Biology: Understanding Normal and Abnormal Development 1 FROM CELLS TO SELVES The Strategic Planning Process During 1998 and 1999, the NICHD staff engaged the This document refines the goals and objectives outlined scientific community in jointly developing a strategic plan under the area titled “Developmental Biology: to facilitate achieving its mission. The initial framework Understanding Normal and Abnormal Development.” document for this plan, From Cells to Selves, highlighted four areas for immediate strategic development and To help establish the more detailed research agenda that described a series of scientific goals under each area. follows, the NICHD convened a working group These four areas were as follows: comprising distinguished scientists (see Appendix) from around the country and asked them to collaborate with • Genetics and Fetal Antecedents of Disease Susceptibility Institute staff to identify and prioritize research goals and includes the interaction of the genotype with to suggest appropriate strategies to meet those goals. socioeconomic, environmental, and psychological The working group drew upon ongoing planning efforts, factors in the fetal and postnatal environment that previous emphasis areas, recent forums, workshops, contribute to health or the pathophysiology of conferences, and research findings to develop a draft of diseases. the strategic plan that would guide the Institute’s research agenda in developmental biology for the next 5 years. • Reproductive Health for the 21st Century comprises the biological and behavioral factors that allow The draft plan was posted on the NICHD Web site to couples to have healthy children when they want them allow members of advocacy groups, nonprofit and the reproduction-related conditions that may organizations, the scientific community, and the general affect women during and after their reproductive public to comment. In addition, the Institute shared the years. plan with members of the National Advisory Child Health and Human Development Council and with the • Developmental Biology: Understanding Normal and Friends of the NICHD, a coalition of more than 100 Abnormal Development consists of the basic biological professional and patient organizations committed to the science necessary to understand early development Institute’s scientific mission. After consolidating and in utero and through the time when many organ reviewing all comments, the NICHD revised and systems form. finalized the plan. This document is intended as a targeted, but flexible, blueprint that can be modified as • Biobehavioral Development includes research to better new scientific findings, research opportunities, or understand the developmental processes involved in resources become available. forming cognitive, learning, emotional, social, and physical behaviors, and the biological and environmental factors that make infants, children, and adolescents more susceptible to behavioral disorders or to adopting risk-taking and violent behaviors. Developmental Biology: Understanding Normal and Abnormal Development 2 FROM CELLS TO SELVES Introduction Although the Institute has made great progress in to care for their disabled children from childhood into preventing infant deaths resulting from low birth weight, adulthood. While there are thousands of different types prematurity, respiratory distress syndrome, and Sudden of birth defects with varying degrees of severity, the Infant Death Syndrome (SIDS), birth defects remain the lifetime costs to the U.S. economy of children born with leading cause of deaths in infants younger than 1 year any of 17 major structural birth defects are estimated to of age, accounting for one of five infant deaths. be more than $6 billion a year. Consequently, the full Estimates indicate that more than 150,000 babies in the economic impact for all birth defects is much greater. United States are born each year with significant birth The emotional costs to families are incalculable. defects (about 4 percent of all live births). Families with babies born with severe, nonfatal birth defects, often Developing effective strategies to prevent birth defects is accompanied by mental retardation, are burdened possible only with a thorough understanding of the financially by expensive special medical treatment, epidemiology, etiology, and pathogenesis of birth education, rehabilitation, and other supportive services defects–areas where tremendous gaps in knowledge still Developmental Biology: Understanding Normal and Abnormal Development 3 FROM CELLS TO SELVES exist. Progress in these areas requires a better of human development. In the context of this strategic understanding of clinical phenotypes, human syndrome plan, the timeframe of development ranges from the delineation, teratogens, epidemiology, and the natural earliest stages of embryonic development, including history of birth defects. Also essential is gaining an in- blastocyst and trophoblast formation, gastrulation, depth understanding of the basic mechanisms that neurulation, and the establishment of the basic body underlie normal developmental processes, through the plan, through organogenesis. In certain cases, such as appropriate use of animal models and stem cell* research dealing with the immune and nervous systems, research. Accomplishing these goals will require a joint studying later stages of development may help scientists effort by clinicians and basic scientists to approach birth to better understand how these systems respond to the defects research from their respective strengths and build environment during the postnatal period. on each other’s progress. Thus, a common theme in the emphasis areas outlined in this strategic plan is the need The sections on Research Technologies and Resources for a two-way flow of information between scientists with and Training and Education address resource and different types of research interests and endeavors. Such training requirements, which the NICHD views to be as collaboration will help to fill the gaps in knowledge vital to the advancement of these research areas as is about how both genetic and environmental perturbations support of basic research itself. The section on Research of normal processes cause developmental abnormalities. Technologies and Resources also capitalizes on and further develops the essential biotechnology from the Findings from clinical studies will also provide insight emerging areas of structural, functional, and and direction to basic scientists studying developmental comparative genomics and proteomics, to unravel the processes. Similarly, translating basic findings from the complex processes of developmental biology at higher use of animal models and stem cell research to relevant levels of resolution. Both the application of this clinical research will increase our understanding of expanding technology and the expected data from the human embryonic development and the formation of Human Genome Project increase the need for support of structural birth defects. infrastructure, bioinformatics, and data presentation. The section on Training and Education highlights the The scientific goals delineated in the following section of need for basic/clinical integrative training, as well as this strategic plan take advantage