NIH Research Highlights

Our Nation's investment in biomedical research—supported primarily through the National Institutes of Health (NIH)—has dramatically improved health outcomes. Americans are now living longer and aging healthier than ever before, thanks in large part to biomedical discoveries made by NIH-funded scientists. Disability rates for American seniors dropped by nearly one-third over the past two decades, death rates from cardiovascular disease have declined by 63 percent over the past 30 years, and in 2006 the absolute number of cancer deaths in the United States dropped for the first time in history. NIH research is currently conducted by nearly 6,000 NIH staff scientists, as well as more than 212,000 researchers across the country and around the world, who are supported by more than 50,000 NIH competitive grants. The following are just a small sampling of the research accomplishments by these NIH-supported scientists in 2006.

Disease Prevention, Diagnosis, and Treatment

• First Vaccine To Prevent Cervical Cancer—An NIH-funded scientific quest spanning nearly two decades ultimately led to U.S. Food and Drug Administration approval for a vaccine to prevent cervical cancer, a disease that claims the lives of nearly 4,000 women in the United States each year. The genetically engineered vaccine —the first vaccine ever approved for use against cancer —protects against infection from the two types of human papillomavirus (HPV) that cause the majority of cervical cancers worldwide.
• First Totally Implanted Permanent Artificial Heart Approved—NIH's nearly half-century commitment to exploring innovative mechanical approaches for treating damaged hearts ultimately led to development of the first totally implanted artificial heart, approved by the U.S. Food and Drug Administration in September 2006. FDA approval is considered a significant milestone, because few options exist for patients with severe heart failure. The new device is intended for patients who are not eligible for a heart transplant and whose life expectancy without the device is only a month.
• Diuretics Better at Preventing Heart Failure—Diuretics are more effective than newer blood pressure-reducing medications in preventing heart failure, at least in the short term, according to an NIH-funded clinical study. Called the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the study evaluated more than 42,000 people with high blood pressure, or hypertension, the leading risk factor for heart failure. The investigators observed that, during the first year of treatment, patients who received the newer, more expensive medications—calcium channel blockers or angiotensin converting enzyme (ACE) inhibitors—were twice as likely to be hospitalized or die from heart failure than those taking the less expensive diuretics. In later years, however, differences between the treatment groups declined.
• Dietary Supplements May Not Help Knee Pain—The popular dietary supplements glucosamine and chondroitin sulfate are commonly used to treat osteoarthritis, an often-painful condition caused by the wear and tear of cartilage in joints. But a four-year national trial sponsored by NIH found that these substances—naturally found in and around cartilage—are usually no more effective than a placebo in relieving osteoarthritis knee pain. A close examination of the 1,600 study participants showed that a small subgroup who had moderate-to-severe pain achieved relief through combined therapy that included both supplements. However, because of the small number of people in the subgroup, the finding needs to be confirmed in a study designed for this purpose. Ongoing research will also examine whether the supplements might slow progression of osteoarthritis.
• Study Questions Artery-Opening Surgery After Heart Attack—Opening up a blocked coronary artery can be life-saving in the first 12 hours after a heart attack, physicians agree. But a large NIH-funded clinical trial challenges the long-held belief that the same artery-opening procedure—known as balloon angioplasty—is also beneficial three or more days after a heart attack. In an international study involving more than 2,100 patients, researchers found that medically stable patients who received drug therapy and angioplasty 3-28 days after a heart attack did no better than those who received drug therapy alone, even after up to 5 years.
• Herb Treatment Ineffective for Menopause Symptoms—The widely used herbal supplement black cohosh is no more effective than a placebo in relieving the hot flashes and night sweats associated with menopause, according to a yearlong clinical study funded by NIH. The 351 study participants—all experiencing daily menopausal symptoms as the study began—were randomly assigned to receive either herbal regimens that included black cohosh; menopausal hormone therapy (estrogen with or without progesterone); or a placebo. Only the hormonal therapy successfully reduced symptoms.
• Inexpensive Drug Can Prevent Postpartum Hemorrhage—Researchers found that the drug misoprostol provides a safe, convenient, and inexpensive way to prevent postpartum hemorrhage, a major killer of women in developing countries, according to NIH scientists and their collaborators. Deaths from postpartum hemorrhage, excessive bleeding by the mother after giving birth, are rare in countries where hospitals and emergency care are readily available, but the condition can be life-threatening in regions where most births occur at home and medical care is harder to come by. In a clinical study conducted in rural villages in India, women who received the drug after birth were less likely to have serious postpartum bleeding, and had significantly lowered average blood loss, than women who received placebo.
• Molecules in Blood Signal Problem Pregnancy—A simple blood test may offer an early warning sign of pre-eclampsia, a life-threatening complication of pregnancy and the world's leading cause of premature birth. NIH-supported scientists found that blood levels of two proteins rise markedly up to three months before the appearance of pre-eclampsia symptoms, including high blood pressure and protein in the urine. Detecting high levels of these proteins may help not only to predict pre-eclampsia but also to distinguish it from other conditions with similar symptoms, including chronic high blood pressure and kidney disease.
• Enhancing Diagnosis of Blood-Cell Cancers—A multinational research team, including several NIH scientists, developed an experimental test that appears more effective than current techniques in distinguishing between two white-blood-cell cancers. Correct diagnosis is critical because the two cancers—Burkitt's lymphoma and diffuse large B-cell lymphoma—require very different treatments. The new diagnostic technique, known as gene expression profiling, simultaneously analyzes more than 2,500 genes to determine which are active in samples of cancerous cells. The two types of lymphoma were found to have distinctive gene expression patterns, allowing the researchers to accurately classify cancers from 71 patients. Further development, however, is needed before the test is ready for clinical use.
• Experimental Medication Kicks Depression in Hours—Current antidepressants usually take four to eight weeks to exert their effects. In a preliminary new study, NIH scientists found that a single intravenous dose of ketamine—a medication usually used in higher doses as an anesthetic—brought symptom relief to people with treatment-resistant depression in as little as two hours. Despite its effectiveness, ketamine is unlikely to be widely used for treating depression because of its potential side effects, including hallucinations and euphoria, at higher doses. Nevertheless, the findings may offer insights toward development of a new class of faster- and longer-acting antidepressant medications.
• Experimental Ragweed Allergy Therapy Uses Fewer Shots—An experimental treatment for ragweed allergies requires fewer injections than standard immunotherapy and leads to a marked reduction in symptoms that lasts for at least a year after therapy has stopped, according to a small clinical trial supported in part by NIH. As many as 40 million Americans suffer from seasonal allergies caused by airborne pollens like ragweed, one of the most common pollens in the United States. The new therapy, which combines a major ragweed molecule with a small DNA strand that stimulates the immune system, requires only six weekly injections. Current ragweed immunotherapy usually involves regular injections administered over several years.
• Blood Test Predicts Complication of Sickle Cell Disease—A hormone detected in a simple blood test can identify patients with sickle cell disease who have developed a life-threatening complication called pulmonary hypertension, according to a clinical study conducted by NIH scientists. The hormone is also a clear predictor of death in adults with sickle cell disease. This experimental test may one day help doctors identify patients for earlier treatment.
• No Apparent Benefit to Monitoring Fetal Oxygen—Electronic fetal monitoring is widely used to track the fetus's heart rate during labor and determine when an emergency Caesarean delivery might be needed. More recently, a technology called fetal oxygen saturation monitoring was developed to measure oxygen levels in fetal blood, in hope that additional health information might prevent problematic births and C-sections. However, an NIH-funded clinical trial involving more than 5,000 women showed that the new technology offers no apparent benefits, and in some cases even caused complications. The oxygen monitoring did not significantly reduce Caesarean delivery rates or improve the condition of infants at birth.
• Smoking Affects Allergy in Infants—Infants as young as 6 months old can become allergic to airborne substances, causing a stuffy nose, sneezing and other symptoms. In a study of the environmental factors that might trigger these allergies, NIH-funded researchers found that exposure to more than 20 cigarettes a day nearly tripled an infant's risk for developing allergies to airborne compounds by age 1. Mold, another suspected culprit, did not increase the allergy risk but did boost susceptibility to for upper respiratory infections. Other factors—like race, gender, pet ownership and breastfeeding practices—did not appear to affect allergy or respiratory infection risk.
• Low-Calorie Diet Affects Aging-Related Factors—Scientists have long known that sustained adherence to low-calorie diets substantially increases the lifespan of several laboratory animals. However, the effects of low-calorie diets on human aging have been unclear. An NIH-funded pilot study now shows that overweight people who cut their calories by 25% for six months have reduced fasting insulin levels and core body temperature, two markers that have been associated with increased longevity in humans. A longer-term clinical trial—conducted at three U.S. locations—will now evaluate the effects of reduced-calorie diets over a longer time period.
• New Imaging Technique May Spot Early Indictors of Alzheimer's Disease—A molecule that binds to abnormal proteins in the brain shows promise for enabling early and reliable diagnosis of Alzheimer's disease, a condition that today can be definitively diagnosed only at autopsy. The molecule, known as FDDNP, was developed and clinically evaluated by researchers supported in part by NIH. After intravenously administering FDDNP, the researchers obtained brain scans that could distinguish among individuals who were healthy, those who had Alzheimer's disease and those who had mild cognitive impairment, which sometimes progresses to Alzheimer's disease. Beyond aiding clinical detection, this new technique may also allow scientists to assess how well potential new Alzheimer's therapies slow or halt the disease's progress.
• Better Detection of Blood Clots in the Lung—Pulmonary embolism, a sudden and potentially deadly blockage in a lung artery, often arises when a blood clot breaks free from the deep veins of the leg and travels to the lung. Early detection and treatment is key, because pulmonary embolism leads to death in nearly a third of untreated cases. An NIH-funded study has shown that doctors can more accurately diagnose pulmonary embolism by combining a commonly used imaging test of the chest with a scan of the leg, where the blood clots typically originate. Pulmonary embolism affects an estimated 600,000 Americans each year, making it the fourth most common cardiovascular problem in the United States.
• Low-Fat Diet's Benefits Unclear in Older Women—Eating a low-fat diet high in fruits, vegetables and grains did not significantly lessen the risk of breast cancer, colorectal cancer or heart disease in healthy older women, according to results from the NIH Women's Health Initiative. Yet examination of the nearly 50,000 postmenopausal women who participated in the study provided some evidence that healthful eating can have certain benefits. For instance, breast cancer risk was 9% lower among women on the low-fat diet, although scientists say this modest difference may have been due to chance.
• Circumcision Reduces Risk of AIDS Virus Infection—Medically performed circumcision significantly reduces a man's risk of acquiring HIV through heterosexual intercourse, according to two NIH-funded clinical trials. The two studies involved a total of nearly 8,000 HIV-negative heterosexual men who were randomly assigned to be circumcised either soon after enrollment or two years later. The trials were halted early, because interim assessment of data clearly indicated that circumcision could reduce the likelihood of HIV acquisition by about 50%.

Genomics and Genetics

• Gene Ups Diabetes Risk, Healthy Lifestyle Lessens Impact—NIH-funded researchers confirmed that a variant gene discovered in early 2006 boosts susceptibility to type 2 diabetes. By examining data from a clinical study involving more than 3,500 individuals, the scientists also found that even people with the highest genetic risk—those who inherited two copies of the variant gene—could make positive lifestyle changes, including exercise and weight loss, that reduce their diabetes risk.
• Researchers Assemble Monkey Genome—A multicenter research team, funded in part by NIH, completed the draft genome sequence of the rhesus macaque monkey and deposited the information into free public databases. The rhesus macaque is the second non-human primate, after the chimpanzee, to have its genome sequenced. Overall, the macaque shares about 92-95% of its genome sequence with humans. Because of this similarity, the rhesus macaque is the principal non-human primate used for the study of human disease and plays an important role in drug and vaccine development.
• Gene Discovered for Brittle Bone Disease—NIH researchers reported that a previously unexplained fatal form of osteogenesis imperfecta (OI)—a rare bone-weakening disorder that can cause frequent fractures—results from a genetic defect in a protein involved in collagen production. This particular form of OI arises when a child inherits two defective copies of the gene. Although there is no treatment for OI, the finding may allow physicians to test for the recessive gene in families who have lost a child to OI. Discovery of the new gene may also lead to insights into the formation of bone and other tissues.
• Pigment Gene Affects Melanoma Risk—NIH scientists have uncovered a complex interaction between two genes that dramatically affects the likelihood of developing melanoma, an aggressive skin cancer. In a study involving nearly 200 Caucasians who had few signs of chronic sun damage, the researchers found that specific variations in a pigment-related gene enhances the risk of developing melanomas that have mutations in a cancer-causing gene known as BRAF. Potential melanoma drugs that target BRAF are now in clinical trials.
• Gene Affects Pain Sensitivity—NIH-funded researchers identified a human gene that affects sensitivity to short-term pain and the risk of developing chronic pain after surgery. The gene produces an enzyme that aids production of neurotransmitters, which deliver signals between nerve cells. The investigators found that chronic pain could be prevented in animals, following nerve injury or inflammation, by blocking increased activity of this gene. The findings point to potential new avenues for treating or preventing chronic pain, which affects as many as 50 million people in the United States.
• Mutant Gene More Than Doubles Susceptibility to Autism—In a family-based study involving more than 1,200 individuals with autism, NIH-funded scientists identified a mutant gene that more than doubles a child's risk of developing an autism spectrum disorder. The normal version of the gene is known to contribute not only to brain development but also to immune and gastrointestinal functions, which are sometimes impaired in children with autism. The implicated mutation creates a tiny variation in the part of the gene that turns it on and off. The mutation cuts the gene's expression by half, presumably impairing brain development.
• Researchers Identify Risk Gene for Obsessive-Compulsive Disorder—NIH scientists have identified a previously unknown gene variant that nearly doubles an individual's risk for obsessive-compulsive disorder (OCD), the fourth most prevalent mental health disorder in the United States. The implicated gene produces a cell-surface molecule that is targeted by popular antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs), which are also used to treat OCD and other anxiety disorders. Improved knowledge of the gene's role in OCD may ultimately aid screening and treatment for the disorder.

New Research Directions

• New Clues About the 1918 Flu Virus—The first comprehensive analysis of an animal's reaction to the 1918 influenza virus provides new insights into this deadly flu, which disproportionately killed young people in the prime of their lives. NIH-funded researchers found that the 1918 virus triggers a hyperactive immune response that may be the key to its lethal effects. The findings also suggest that all eight of the genes found in the 1918 virus help to make it so deadly. A deeper understanding of the 1918 virus will likely aid efforts to develop improved therapies against related viral threats, including the H5N1 avian influenza virus.
• Insight into Ear Infections—Chronic infection or inflammation of the middle ear, the area just behind the eardrum, is a common, often-recurring problem for children. A new study by NIH-funded scientists shows why the problem can be so persistent: bacteria can form a "biofilm" on the middle ear that helps them resist the body's immune system and antibacterial treatments. Because biofilms also play a role in other types of persistent infections, researchers are now investigating how bacterial biofilms form and how they elude antibiotics and other defenses.
• Watching Nicotine at Work in the Brain—A brain imaging study supported in part by NIH shows how the nicotine in just a few puffs of a cigarette can drive someone to continue smoking. The amount of nicotine in just one puff of a cigarette occupied about 30% of the brain's most common type of nicotine receptors, while three puffs of a cigarette occupied about 70%. Only when nearly all of the receptors were occupied, after smoking at least two and a half cigarettes, did the smokers becomes satiated, or satisfied, for a time. By better understanding how nicotine affects the brain, scientists hope to develop improved therapies for smokers who would like to quit.
• Restoring Function to Paralyzed Rats—Researchers used a novel technique involving embryonic stem cells to partially restore muscle function to paralyzed animals. With funding from NIH and other sources, the scientists cultured mouse embryonic stem cells with chemicals that triggered transformation into muscle-stimulating nerve cells, which were then transplanted into the spinal cords of rats. The transplants ultimately produced numerous connections between nerve and muscle cells, which improved muscle function in the paralyzed animals. Although the results are promising, much work remains before a similar strategy could be tried in humans.
• Elusive Sour Taste Cells Revealed—NIH scientists and their colleagues identified specialized taste cells on the tongue that detect sour flavors and may help to warn people and animals of acidic, spoiled and unripe food. The researchers had previously pinpointed the distinctive cell sensors that can detect sweet, bitter and umami (the taste of monosodium glutamate). Now only one mammalian taste-sensing cell is yet to be discovered—that for salty taste.
• Hints of Language Origin in Rhesus Monkey—Fossil records can't tell us where the building blocks of language appeared on the evolutionary timeline, but brain imaging might. Studies by an international research team, including NIH-funded scientists, revealed that, when contemplating the coos and screams of a fellow member of its species, the rhesus monkey (or macaque) uses brain regions that correspond to the two principal language centers in the human brain. The results suggest that a shared ancestor to humans and the macaque may have had the neural mechanisms upon which language was built.
• Unique Technique Improves Vision of Blind Mice—NIH-funded researchers are developing an inventive approach to restore vision to eyes that have lost their ability to detect light. The scientists studied mice that had been genetically bred to lose rods and cones, the light-sensitive cells in the retina of the eye. As rods and cones die, the mice go progressively blind, similar to the human blinding disease retinitis pigmentosa. Using gene transfer, the researchers restored some vision to the mice by inserting a light-absorbing protein into retina cells that normally do not detect light. The study raises the possibility of improving visual function, even after rods and cones have died, by making other cells in the retina sensitive to light.
• Bullied Mice Shed Light on Social Stress—By studying fearful mice that have been repeatedly bullied by bigger mice, NIH-funded scientists identified a brain molecule and circuitry that contribute to long-lasting social aversion. The researchers also showed that blocking the production or activity of this molecule, known as brain-derived neurotropic factor, can counteract the social aversion caused by aggressive encounters. The findings offer new insights into the molecular pathways that affect social motivation and may aid development of new antidepressants.
• Botulism Toxin's Fatal Grip—Botulism toxins, produced by bacteria, are among the most potent and lethal known poisons. The toxins cause botulism, a sometimes-fatal muscle-paralyzing disease, and are potential bioterror agents. To better understand how the botulism toxin operates, two NIH-supported research teams used advanced technologies to see unprecedented details of the poisonous molecule latching onto nerve cell proteins. The studies revealed new information about a how the toxin specifically grasps onto muscle-activating nerve cells and ultimately blocks communication at the junction where nerve and muscle cells meet. The new findings may aid in the development of more effective therapies or even a vaccine to prevent the neurotoxin's harmful effects.
• A Promising Strategy for Artificial Bone—NIH-supported scientists harnessed the unique physics of sea water as it freezes to guide the production of what could be a new generation of biocompatible materials for artificial bone. The researchers used a novel freezing technique to produce a thin-layered structure that closely mimics the natural scaffolding of bone. The scientists said their prototype scaffolds are ultra-lightweight and up to four times stronger than current porous ceramic implant materials.

Prepared by Vicki Contie
Edited by Harrison Wein, Ph.D.
January 2007