NICHD's Broad Mission Spans Disciplines, Stages Of Life

Sidebar: National Institute on Child Health and Human Development (NICHD) - For More Information ALL FOR ONE: "Our unifying theme is human development in all its aspects," explains NICHD director Duane Alexander. Since its founding nearly 35 years ago, the National Institute of Child Health and Human Development (NICHD) has undertaken an unusually broad mission. Rather than focus on a single disease, organ system, or stage of life, as do most other institutes of the National Institutes of Health, NICHD supports and conducts research in diverse disciplines-for example, biophysics and social psychology-on topics that shape human life. "Our unifying theme is human development in all its aspects," explains NICHD director Duane Alexander. "We look across the spectrum from prenatal phenomena to pregnancy and perinatology to childhood diseases to learning and behavioral development." Such breadth has always marked NICHD. In fact, it required an act of Congress in 1962 to establish an Institute of Health so unlike its predecessors, says Alexander. (At that time, government procedures prohibited double letters in official acronyms, thus the missing "H" in the institute's abbreviation.) High United States infant mortality rates, as well as President John F. Kennedy's experiences with his sister's mental retardation, sparked the institute's creation. National Institute on Child Health and Human Development P.O. Box 29111 Washington, D.C. 20040 (301) 496-5133 Fax: (301) 496-7101 http://www. nichd.nih.gov For information on the more than 100 scientific and medical societies and health advocacy groups connected with NICHD research, contact Friends of the NICHD, a coalition that lobbies for the institute's goals: Friends of the NICHD Susan Persons, Chair Director of Government Relations American Psychological Society 1010 Vermont Ave., Suite 11 Washington, D.C. 20005 (202) 783-2077, Ext. 3012 Fax: (202) 783-2083 E-mail: spersons@capcon.net Along with research on the prevention and treatment of childhood disorders, NICHD promotes efforts to understand normal development at all levels, "from the single cell to the complex organism," says Alexander. The institute also disseminates public health information. For example, its "Back to Sleep" campaign-to reduce the risk of sudden infant death syndrome (SIDS) by placing babies on their backs to sleep-has helped decrease SIDS incidence in the U.S. by 30 percent since 1992. With a 1997 budget of more than $631 million, NICHD ranks approximately eighth in funding appropriations among the institutes. Of that amount, about $524 million, or 83 percent, goes to extramural grants and contracts. These are administered by three subdivisions of the institute: the Center for Population Research, the Center for Research for Mothers and Children, and the National Center for Medical Rehabilitation Research. Another $79 million-more than 12 percent-supports NICHD's extensive intramural research program. Current areas of emphasis include premature labor and low birth weight, vaccine and contraceptive development, pediatric AIDS, learning disabilities, mental retardation, and devices for medical rehabilitation, according to Alexander. "The institute also funds extensive intramural and extramural basic research on the genetic control of early development, and its relationship to birth defects." Recent advances in developmental and molecular biology, Alexander observes, "are really driving these thriving programs." Premier Intramural Program While NICHD-sponsored extramural programs run the gamut from grants for basic studies and clinical trials to contracts for commercial development of medicines and devices, intramural research focuses largely on basic and clinical investigation, according to the institute's scientific director, Arthur S. Levine. An important goal of the intramural programs, he says, is to describe biological and behavioral development in detail. "We feel that most human diseases and disorders have their origins in events that happen during development, whether their cause is genetic or environmental," Levine explains. "A firm understanding of developmental processes will allow us to practice the ultimate form of preventive medicine." The Division of Intramural Research has a staff of about 900, most of whom conduct research in one of 85 independent groups. The division sponsors clinical research and training programs in genetics, endocrinology, and maternal-fetal medicine, as well as developmental studies in scores of laboratories. Among the many scientists pursuing basic research at NICHD, Igor Dawid, chief of the laboratory of molecular genetics, studies development in the frog Xenopus laevis. The animal has provided several valuable insights into early embryogenesis in vertebrates, he reports; over the past decade he and others have used the frog to learn how signaling molecules and transcription factors induce undifferentiated cells to form patterns of specialized cells, and eventually develop into organs. Similarly, Heiner Westphal, chief of the laboratory of mammalian genes and development, uses genetically altered mice to identify molecules that play key roles in mammalian embryogenesis. Recently, researchers in his laboratory described the influence of the molecule Sonic hedgehog on brain, spinal cord, and limb formation in the mouse (C. Chiang et al., Nature, 383:407-13, 1996). Sonic hedgehog-which Westphal calls "the developmental biology molecule of the year"-is also known to influence embryonic pattern formation in organisms ranging from worms to humans. FINDING GENETIC SECRETS: Research by Domenico Accili and collegues shows two genes may be the root of diabetes mellitus Westphal's laboratory also develops mouse models of human diseases, including neoplasias, single-gene hereditary disorders, and diabetes. The last of these is the special interest of Domenico Accili, chief of the clinical research unit on genetics and hormone action. He creates mouse models of the genetically complete adult-onset form of diabetes mellitus, known as NIDDM (for non-insulin-dependent diabetes mellitus). "For years, people have struggled to locate candidate genes [underlying NIDDM] . . . but no major gene has been identified," he explains. Thinking that the disease might result from a combination of mutational "hits" to several different genes, Accili and coworkers attempted to re-create diabetes symptoms by producing transgenic mice with multiple mutations. First, the researchers created a mouse predisposed to insulin resistance, a metabolic abnormality often found in diabetic patients, by knocking out the insulin receptor gene (D. Accili et al., Nature Genetics, 12:106-9, 1996). This result, Accili says, indicates that the receptor exerts "a very large effect for a complex disease." And in the February 21 issue of Cell (J.C. Brüning et al., 88:561-72, 1997), Accili and collaborators at Harvard University presented evidence that mice with reduced expression of both the insulin receptor and IRS-1 gene, which controls the cellular response to insulin, mimic patterns of NIDDM inheritance. "Just two genes could account for the entire susceptibility to this complex disease," concludes Accili. Animal models also illuminate research on behavioral, cognitive, and psychological development in the Laboratory of Comparative Ethology. There, scientists study rhesus and capuchin monkeys to determine why individual differences in primate behavior arise early in development, what their consequences are, and whether parents can influence their expression, according to lab chief Stephen J. Suomi. The monkeys are selectively bred to study the heritability and neurobiological characteristics of behaviors such as response to novelty or stress, he explains. MARKED QUALITY: NIH’s Michael Gottesman notes that NICHD’s researchers are among "the most highly cited basic scientists." NICHD intramural researchers also include John Robbins and Rachel Schneerson, winners of the 1996 Albert Lasker Clinical Medical Research Award for their contributions to the development of an effective vaccine for Haemophilus influenzae type b (K.Y. Kreeger, The Scientist, Oct. 28, 1996, page 3). "The NICHD intramural program is nothing short of spectacular," states Michael M. Gottesman, deputy director of intramural research for NIH. "It includes some of the most cited basic scientists in biomedical research and shows no sign of diminishing in quality." Of the three NICHD divisions that fund extramural research, two-the Center for Population Research (CPR) and the National Center for Medical Research and Rehabilitation (NCMRR)-were founded years after the institute's creation in response to public concerns regarding overpopulation and people with disabilities. The smallest of the extramural research centers, NCMRR was established in the early 1990s to promote health and quality of life for the disabled. Research funded by the center includes behavioral studies of rehabilitation following stroke or brain injury, development of novel assistive technologies, and gene therapy for neurological regeneration. Several NCMRR-funded extramural researchers are also exploring ways to produce replacement tissues for damaged body parts or diseased organs. Among them, molecular biologist Malcolm S. Steinberg of Princeton University studies the molecular interactions that determine how cells and tissues organize themselves into organs. In two recent publications (R.A. Foty et al., Development, 122:1611-20, 1996; M.S. Steinberg, M. Takeichi, Proceedings of the National Academy of Sciences, 91:206-9, 1994), he and coworkers have described how measurable, predictable cellular adhesions lead to the envelopment of one layer of embryonic tissue by another. As the threat of global overpopulation became increasingly apparent in the late 1960s, CPR was founded to address a variety of population issues. Today, the center continues to support research on the causes and consequences of population change, contraception, and biomedical studies of human reproduction. Not all of that work is directed specifically toward population control, however. Several projects sponsored by the reproductive sciences branch could have the opposite benefit of circumventing infertility, says branch chief Michael McClure. In addition to funding two infertility centers at the University of Pennsylvania and Massachusetts General Hospital, the branch supports research on both male and female infertility. A recent spate of NICHD-sponsored discoveries marked 1996 as "the year of the male," McClure reports. These include the first techniques for manipulating and transplanting undifferentiated sperm stem cells, and the identification of genes involved in sperm insufficiency. In addition, reproductive biologist Ryuzo Yanigamachi of the University of Hawaii at Honolulu received the 1996 Japan Prize-that nation's equivalent of the Nobel-for the first use of a intracytoplasmic sperm-injection technique to fertilize an egg with a single immature sperm, known as a secondary spermatocyte. The method has promise for clinically reversing infertility among males whose sperm fail to completely develop and in animal husbandry. REPRODUCTION RESEARCH: Washington’s David Battaglia is examining subcellular events that lead to Down syndrome. Among extramural researchers studying female reproduction, David Battaglia, an assistant professor of obstetrics and gynecology of the University of Washington Health Science Center, is examining the subcellular events that lead to Down syndrome and related chromosomal abnormalities linked to maternal age. These birth defects result from an uneven distribution of chromosomes during meiosis, which occurs monthly as egg follicles mature. "What we've found," says Battaglia, who directs the Washington Fertility and Endocrine Center Laboratory, "is that the meiotic spindle -the machine that manages chromosomes-is often very seriously broken in older women." What breaks the meiotic machine? "Our main theory is that as women age, hormonal imbalances in the environment in which the follicles mature . . . somehow damage the meiotic spindle," Battaglia replies. Eventually, he says, scientists may be able to remove follicles from older would-be mothers for maturation and fertilization in vitro, then return embryos to their uteri. NEW CONTRACEPTIVES?: Virginia cell biologist John Herr is working to develop antigen-based contraceptives. Meanwhile, scientists at two NICHD-supported contraceptive vaccine development centers at the University of California, Davis, and the University of Virginia are working to develop novel birth-control methods. The researchers are isolating proteins that are found only on the surface of sperm and egg cells, or on the zona pellucida, a cloud of cells that surrounds the unfertilized egg. The scientists eventually hope to administer such proteins to women, whose immune systems would produce antibodies that could interfere with fertilization without provoking an autoimmune reaction. "We're trying to develop antigen-based contraceptives to be delivered by classical immunization or through a slow-release formulation," says Virginia cell biologist John C. Herr. Reflecting the overall breadth of NICHD, the Center for Research for Mothers and Children (CRMC) funds extramural research through eight branches. Diverse areas of study within the center include developmental biology; pregnancy and perinatology; pediatric, adolescent, and maternal AIDS; endocrinology and nutrition; and human learning and behavior. Researchers funded by CRMC include 1995 Nobel Prize winners Edward Lewis of the California Institute of Technology and Eric Weischaus of Princeton University. The molecular biologists, along with Christiane N^ßsslein-Volhard of the Max Planck Institute for Developmental Biology in Tübingen, Germany, were honored for their work on genes that control embryonic development in the fruit fly, Drosophila (K.Y. Kreeger, The Scientist, Nov. 13, 1995, page 1). And last December, CRMC grantees Lee Niswander of New York's Memorial Sloan-Kettering Cancer Center and Ali Hemmati-Brivanlou of Rockefeller University were among 60 federally funded scientists who received Presidential Early Career Awards for Scientists and Engineers. Niswander studies embryonic limb formation; Hemmati-Brivanlou examines early processes that control central nervous system development. Several CRMC branches support basic research on perinatal and childhood disorders, including conditions as diverse as premature labor and dyslexia. For example, William Larsen, a professor of cell biology, neurobiology, and anatomy at the University of Cincinnati College of Medicine, studies gap junction formation between the layers of smooth muscle that form the uterine wall. These junctions, he explains, assemble just before labor begins and serve as electrical synapses; they are required to synchronize effective uterine contractions. PERINATAL STUDIES: William Larsen’s work on gap junction assembly may lead to drugs that help prevent premature labor. Gap junction assembly "could provide a kind of ultimate signal to labor," Larsen observes. By understanding this labor-inducing pathway, he and coworkers hope to develop new tocolytic (labor-arresting) agents that would interfere with gap junction formation. "Current tocolytic agents aren't very effective," he notes. "They can only prevent labor for a day or two, but that might be long enough to treat patients with a drug that inhibits gap junction synthesis." 'REMARKABLE' PROGRESS: Research on learning disabilities has come far with NICHD’s support, maintains Yale’s Sally Shaywitz. Thanks to advances in neuroimaging, even learning disabilities-particularly reading disabilities such as dyslexia-are now amenable to study at the neurobiological level, according to G. Reid Lyon, chief of CRMC's learning disabilities, cognitive and social development branch. Recent work by pediatricians Sally Shaywitz and her husband/partner, Bennett Shaywitz, with colleagues at Yale University's Center for the Study of Learning and Attention has begun to pinpoint areas in the brain responsible for discrete steps in the complex task of reading (for an overview, see S. Shaywitz, Scientific American, 275:98-104, 1996). Using a noninvasive technique called functional magnetic resonance imaging (fMRI), she and her coworkers can track activity in different parts of subjects' brains while they attempt various reading tasks. The researchers recently demonstrated functional differences in brain activity between men and women as they read nonsense words (B.E. Shaywitz et al., Nature, 373:607-9, 1995). Now the Yale scientists are conducting intensive longitudinal studies to learn how brain activity changes between ages four and 18 in unimpaired as well as learning-disabled children. Sally Shaywitz reports that they are also monitoring children via fMRI as they're taught strategies to overcome dyslexia to see if neurological changes accompany their progress. Such complex and sophisticated investigations are necessary if researchers hope to understand what really happens in brains with reading disabilities, she says. "We couldn't have studied dyslexia on such a large scale without NICHD support. "It's remarkable how far we've come in the 10 years since the NICHD began supporting centers for learning disabilities research," she recalls. Yale's was the first. At that time, no good definitions for reading disabilities existed. Today, she says, "the fact that we can talk about interventions [to overcome reading disabilities] and actually look at people's brains while they're reading represents a spectacular leap forward for children and children's health." Alison Mack is a freelance science and medical writer based in Wilmington, Del.

NICHD's Broad Mission Spans Disciplines, Stages Of Life

Interested in reading more?

Become a Member of