Selected Research Advances of NIH
NIH has trained a host of scientists in its intramural programs and supported the training of hundreds of thousands of scientists at universities and medical schools around the country through research grants. These scientists have gone on to become leaders in biomedical research at universities and companies around the country, fueling a great many advances in the understanding and treatment of human diseases. What follows is only a sampling of the scientific advances supported by NIH in the past years. The most recent Research Advance is now linked to the current NIH Research Matters
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The 2014 Ebola outbreak in West Africa is the largest such outbreak in history. More than 17,000 cases and 6,000 deaths have been reported. NIH-funded scientists used genomic sequencing technologies to identify the origin and track transmission of the Ebola virus in the current outbreak. Other NIH-funded researchers used computer model projections to provide insight into the dynamics of the outbreak. NIH has also intensified efforts to develop a protective vaccine. The vaccine was tested at the NIH Clinical Center, which also provided state-of-the-art care to a nurse who had contracted the Ebola virus.
Stem Cell Transplant Reverses Sickle Cell Disease in Adults
There is no widely available cure for the inherited blood disorder sickle cell disease. Some children have been successfully treated with blood stem cell, or bone marrow, transplants. This approach was thought to be too toxic for adults. NIH researchers successfully treated adults with severe sickle cell disease using a modified stem cell transplant approach that doesn’t require extensive immune-suppressing drugs. Further follow-up and testing will be needed to assess the therapy.
PROMISING MEDICAL ADVANCES
An Atlas of the Developing Human Brain
The structure and function of the human brain is guided by gene expression patterns during prenatal development. NIH-supported scientists detailed the first comprehensive 3-D atlas of gene expression in the developing human brain. The resource will help reveal the early roots of brain-based disorders such as autism and schizophrenia.
Researchers often turn to model organisms in order to understand the complex molecular mechanisms of genome function. By analyzing the genomes of humans, flies, and worms, NIH-funded scientists uncovered many common, key features. The findings offer insights into embryonic development, gene regulation, and other biological processes that are vital to human biology and disease. The mouse in particular has long been used to gain insights into gene function, disease, and drug development. An international group of researchers funded by NIH gained insights into how similarities and differences between mice and people arise from their genomes. The findings will help scientists better understand how and when mouse models can best be used to study human biology and disease.
Insights from the Lab
Method Can Target Specific Microbes
NIH-funded scientists designed a way to target and destroy specific DNA sequences in microbes, thus removing harmful bacterial genes. The team took advantage of a system called the CRISPR-Cas immune system, which bacteria use to protect themselves against invaders. The researchers modified the system to target genetic sequences associated with bacterial virulence or antibiotic resistance. The approach could be used to develop therapies against pathogenic bacteria, including those resistant to multiple antibiotics.
Immune Cells in Heart Help it Mend
The heart of a newborn has a much greater capacity for repair than that of an adult. A team of NIH-funded scientists thought this might be due to different populations of macrophages, a type of immune cell found in tissues such as the heart. The researchers discovered that the hearts of mice have distinct macrophages that play a key role in recovery from damage. The findings suggest that potential treatment strategies for heart failure might target macrophages.
Malaria Vaccine Found Safe and Protective
Malaria kills hundreds of thousands of people each year, most of them young children in Sub-Saharan Africa. While scientists have made significant gains in understanding, treating, and preventing the disease, a vaccine has remained elusive. NIH researchers reported that a candidate malaria vaccine is safe and protected against infection in an early-stage clinical trial.
Duration of Obesity May Affect Heart Disease
Past research has linked obesity to heart disease risk. But few studies have examined how the duration of obesity affects heart disease. NIH researchers found that how long a young adult is obese may affect that person’s heart disease risk in middle age. The finding suggests that not only preventing but also delaying the onset of obesity can help reduce heart disease later in life.
Promising Medical Advances
Insights into Brain Injury
Concussions can have serious and lasting effects. However, the specific damage that occurs in affected brain tissue hasn’t been well understood. A study by NIH researchers provided insight into the damage caused by mild traumatic brain injury and suggested approaches for reducing its harmful effects.
Strategy May Improve Survival after Shock
Shock is a life-threatening condition in which blood pressure drops and not enough blood and oxygen can get to organs. Inflammation has been strongly linked with shock, and past research suggests that this inflammation involves the digestive system. An NIH-funded study of rats found that blocking digestive enzymes in intestines increases survival, reduces organ damage, and improves recovery after shock. The approach may lead to new therapies to improve patient outcomes.
Insights from the Lab
Seeing Into the Brain
Scientists seeking to understand the brain’s fine structure and connections have been faced with tradeoffs. To examine deeply buried structures, they had to cut brain tissue into extremely thin sections. This deforms the tissue and makes it difficult to study brain wiring and circuitry. NIH-funded scientists developed a new technique to preserve the brain’s 3-D structure down to the molecular level with a hydrogel. It allows for study of the brain’s inner workings at a scale never before possible.
Scientists Recode Organism's Genome
Living microbes can quickly and reliably produce proteins, the building blocks of the cell. This ability has long been harnessed to produce conventional proteins, such as insulin, for medical use. Synthetic biology seeks to redesign natural biological systems for new purposes. NIH-funded researchers developed a method to recode a bacterium’s genome to incorporate synthetic non-standard amino acids into its proteins. The technique can potentially turn microbes into efficient living factories that make novel compounds.
How Often Should Women Have Bone Tests?
Experts recommend that older women have regular bone density tests to screen for osteoporosis. But it had been unclear how often to repeat the tests. An NIH-supported study of nearly 5,000 women reported that patients with healthy bone density on their first test might safely wait 15 years before getting rescreened. These findings can help guide doctors in their bone screening recommendations.
How Sulfa Drugs Work
Scientists finally found out how sulfa drugs—the first class of antibiotics ever discovered—work at the molecular level. The NIH-supported finding offers insights into designing more robust antibiotic therapies that also avoid side effects and other problems associated with sulfa drugs.
Promising Medical Advances
Egg-Producing Stem Cells Found in Women
Researchers long believed that women are born with a fixed number of young egg cells, or oocytes, that must last through their reproductive years. NIH-supported scientists were able to isolate egg-producing stem cells from the ovaries of women and observe these cells giving rise to oocytes. The finding may point the way toward improved treatments for female infertility.
Gene Therapy Restores Sense of Smell in Mice
Mice that were unable to smell from birth gained the ability to smell when NIH-funded researchers used gene therapy to regrow structures called cilia on cells that detect odor. The approach might one day lead to treatments for related human genetic disorders.
Insights from the Lab
Finding Treasure in "Junk" DNA
A worldwide research consortium created a view of the human genome that extends well beyond our genes. The NIH-funded ENCODE project involved over 1,600 sets of experiments on 147 types of tissue. Scientists catalogued many aspects of gene regulation that can affect function. The project’s ultimate goal is to identify all functional elements in the human genome, including genes and the DNA in between.
Looking Inside Viruses
Cryo-electron microscopy uses radiation to look at the surfaces of viruses, but radiation can destroy the tiny structures within. NIH-supported scientists turned the problem of radiation damage into an asset by taking and then superimposing many “snapshots” of viruses under increasing doses of radiation. They used the technique to clearly visualize the inner structure of a virus. The method may yield insights that suggest new therapeutic strategies.
Less Invasive Surgery Just as Effective for Some Breast Cancer Patients
When breast cancer has spread to nearby lymph nodes, many doctors believe that removing several more nodes provides better treatment. But an NIH-funded study found no difference in survival rates 5 years after surgery, whether patients had had about 2 or more than 10 lymph nodes removed. The finding may change the way early-stage breast cancer is treated in some patients.
Trial Restores Movement to Paralyzed Man's Legs
Specialized physical therapy and electrical stimulation to the spine enabled a man with a spinal cord injury to stand and move paralyzed muscles. After 2 years of physical therapy alone, doctors supported by NIH implanted electrodes in the paralyzed man's spinal cord. With electrical stimulation from the electrodes, the patient now has control of previously paralyzed muscles below the site of injury.
PROMISING MEDICAL ADVANCES
Why Nicotine is a Gateway Drug
An NIH-funded study in mice showed how tobacco products may act as gateway drugs, opening the door for cocaine use. Researchers found that mice given nicotine for 7 days had specific changes in the brain that also occur with cocaine addiction. Mice with these changes had stronger reactions to subsequent cocaine use. The finding hints that lowering smoking rates might help reduce cocaine abuse.
Gene Therapy Helps Patients with Hemophilia
Scientists reported that a single dose of an experimental gene therapy boosted production of a missing blood-clotting factor in people with hemophilia. In an NIH-funded study, 6 patients with severe hemophilia received infusions of a modified virus carrying a normal gene for the blood-clotting factor. After treatment, all the patients had higher levels of the factor in their blood, and 4 of the 6 patients no longer needed regular infusions of the blood-clotting factor to treat bleeding.
INSIGHTS FROM THE LAB
Sleep-Deprived Neurons Caught Nodding Off
A new study gave insight into the roots of sleepiness. When NIH-funded researchers deprived rats of sleep, they caught neurons in the thinking part of the animals' brains taking catnaps. The longer the rats were awake, the more neurons they saw having brief “off” periods, which was linked to more difficulty touching a target. The study suggests that lowered performance in tired people might be due to neurons nodding off.
Genome Comparison Casts Light on Dark Areas of DNA
A massive NIH-supported effort to sequence and compare 29 mammalian genomes shed new light on the “dark matter” of the genome, the over 98% of DNA that doesn't code for proteins. Scientists found that 5% of the genome is more similar than expected, or “constrained” by evolution. The study revealed previously undiscovered DNA segments that code for RNA and protein, and millions of other elements that may control gene expression.
Alzheimer’s Disease Signature Seen in Spinal Fluid
Levels of 2 proteins in cerebrospinal fluid might be used to identify people with Alzheimer's disease before they show clinical symptoms. A distinct Alzheimer's signature—reduced levels of a specific beta-amyloid protein and increased levels of a phosphorylated tau protein—was found in 90% of Alzheimer's patients and 72% of people with mild cognitive impairment. The NIH-funded finding could open new opportunities for developing Alzheimer’s therapies.
Best Treatment Differs for Kids With Asthma
Most children who have trouble controlling their asthma with low-dose inhaled corticosteroids show improvement by increasing the dose or adding another medication, an NIH-funded study reported. However, the best option differed for each child. The clinical study of over 150 children identified characteristics, such as ethnicity, that raise the likelihood of one treatment working better than another. The finding highlights the need for a personalized approach to treating pediatric asthma.
PROMISING MEDICAL ADVANCES
Progress on a Universal Flu Vaccine
NIH researchers developed a method to generate antibodies that attack a diverse array of influenza viruses in animals. The success moves scientists closer to a universal flu vaccine—one that protects against multiple viral strains for several years. After receiving a vaccine that targets a particular viral protein, followed by a booster shot, animals produced broadly neutralizing antibodies. Most were protected from death after exposure to the deadly 1934 flu virus.
Cholesterol Genes Tied to Age-Related Macular Degeneration
By analyzing the genomes of more than 18,000 people, NIH-funded scientists identified 3 new genes associated with the blinding eye disease age-related macular degeneration (AMD). Two of the genes are involved in the cholesterol pathway—a formerly unknown biological mechanism for AMD disease development. The finding raises the possibility that new treatment or prevention approaches might target these genes or pathways.
INSIGHTS FROM THE LAB
Structure of Receptor Involved in Cancer, HIV Infection
NIH-funded scientists determined the 3-dimensional structure of a protein involved in HIV infection and many forms of cancer. Using X-ray crystallography, the scientists captured snapshots of the protein, called CXCR4, bound to molecules that inhibit its activity. The images reveal how CXCR4 molecules form closely linked pairs, with inhibitors bound to their sides. The accomplishment could point to ways of locking out HIV and stalling cancer's spread.
Stress Hormone Causes Epigenetic Changes
Researchers found that chronic exposure to a stress hormone altered DNA in the brains of mice, prompting changes in gene expression. NIH-supported scientists found that giving mice a stress hormone caused epigenetic modifications—changes to DNA that don’t alter sequences but influence gene expression—to a gene that has been tied to posttraumatic stress disorder and mood disorders in people. The finding provides clues into how stress might affect behavior.
DISEASE PREVENTION, DIAGNOSIS, AND TREATMENT
Weight Loss Depends on Less Calories, Not Nutrient Mix
Heart-healthy diets that reduce calorie intake—regardless of differing proportions of fat, protein or carbohydrate—can help overweight and obese adults achieve and maintain weight loss, according to an NIH-funded study. Over 800 adults were assigned to 1 of 4 diets that reduced their calorie intake and contained various levels of fat, protein and carbohydrate. All 4 groups achieved similar weight loss after 6 months and also after 2 years.
Neighborhood Food Options Linked to Obesity in Big Apple
Nearly one-third of adults nationwide are obese. One contributing factor may be the "built environment"—that is, access to stores that sell healthy foods and to resources that support physical activity. An NIH-funded study looked at data on over 13,000 residents of New York City. The scientists showed that ready access to healthy food outlets such as supermarkets and natural food stores was significantly linked to reduced weight status.
PROMISING MEDICAL ADVANCES
Overlooked "Brown Fat" Tied to Obesity
Babies have a type of fat called brown fat, but scientists thought it disappeared by adulthood. NIH-funded researchers showed that not only do adults have it, but it may be important to weight control. Brown fat burns up chemical energy to create heat. Whole-body scans of about 2,000 adults found that the less brown fat tissue they had, the higher their body mass index tended to be.
Lack of Sleep Linked to Alzheimer's Plaques in Mice
People with Alzheimer's disease often have trouble sleeping. A new study suggested that sleep problems may actually contribute to the disease. Alzheimer's disease is marked by dense "plaques"—made mostly of a protein called amyloid-beta—forming between brain cells. NIH-funded researchers found that disrupted sleep can lead to buildup of these plaques in mice. Amyloid-beta levels in both mice and people naturally fluctuate, they discovered, rising while awake and falling during sleep.
INSIGHTS FROM THE LAB
Catching Flu's Drift
Influenza viruses evade the immune system by constantly changing the shape of their outer proteins. New findings by NIH researchers yielded insights into the evolutionary forces that drive this shape shifting, or antigenic drift. If their model is correct, vaccinating more children against influenza could slow the rate of antigenic drift and extend how long seasonal flu vaccines remain effective.
Scientists Detect Key Proteins Needed for Ovulation
Ovulation—the release of a mature egg from an ovary—results from a complex series of biochemical events that aren't fully understood. NIH-funded researchers have identified 2 proteins that are essential for ovulation in mice. The finding not only advances our understanding of ovulation; it may one day lead to new treatments for infertility as well as new ways to prevent pregnancy by blocking release of the egg.
DISEASE PREVENTION, DIAGNOSIS, AND TREATMENT
Dietary Supplements Fail to Prevent Prostate Cancer
Two large NIH-funded clinical trials found that taking vitamin E, vitamin C or selenium does not reduce the risk of prostate cancer or other cancers in older men, as some previous studies had suggested. The results highlight the fact that dietary supplements can sometimes seem beneficial in small observational studies, but large, carefully controlled trials are needed to test whether they really live up to their hoped-for benefits.
Increased Allergen Levels in Homes Linked to Asthma
A little housecleaning may help to reduce asthma symptoms in people who have both asthma and allergies, suggests a study by NIH scientists and their colleagues. A survey of more than 2,500 people showed that allergy-triggering substances, called allergens, were common in most homes. Households with asthmatic people were more likely to have higher levels of multiple allergens, including those from dog, cat, mouse and dust mite.
PROMISING MEDICAL ADVANCES
Gene Variations Linked to Kidney Disease in African Americans
For the first time, researchers have identified genetic variations that are strongly associated with certain kidney diseases that disproportionately affect African Americans. The results of this NIH-funded research may eventually lead to new therapies or diagnostic tools to identify people at higher risk various types of kidney disease.
Map of Structural Variation in the Human Genome
NIH-funded researchers produced the first sequence-based map of "structural" variations in the human genome, including gains, losses and rearrangements of long stretches of DNA. Structural variations have already been linked to HIV susceptibility, coronary heart disease, schizophrenia and autism. The map will help researchers better understand how these variations contribute to human health and disease.
INSIGHTS FROM THE LAB
Novel Type of Antibody Inhibits HIV Infection
NIH scientists identified a small antibody fragment that’s highly effective at neutralizing the human immunodeficiency virus (HIV). The antibody strongly binds to different versions of the HIV envelope protein and prevents a wide range of HIV strains from entering immune cells. The finding may ultimately lead to new therapies against HIV and other viruses.
Prepared by Vicki Contie
Edited by Harrison Wein, Ph.D.
DISEASE PREVENTION, DIAGNOSIS, AND TREATMENT
Established Drug Bests Newcomer in Treating Female Infertility
Researchers reported that infertility arising from polycystic ovary syndrome (PCOS) is better treated with an established ovulation-inducing drug (clomiphene) than with an increasingly popular alternative (metformin). The NIH-funded study was the largest, most comprehensive effort to date comparing the 2 drugs' abilities to promote pregnancy in women with PCOS, a hormonal disorder that affects about 1 in 15 women and is the leading cause of infertility.
Treating Depression in Patients with Bipolar Disorder
Patients with bipolar disorder have severe mood swings between mania and depression. Treatment typically involves mood-stabilizing drugs like lithium or valproate. Two separate reports—both part of a large-scale NIH-funded study of bipolar disorder—looked at how well patients with depression responded when additional treatments were added to their mood-stabilizing therapy. One found that adding an antidepressant medication was no more effective than a sugar pill in reducing depression. (NIH press release | PubMed). The other reported that patients tended to get well faster and stay well if they received intensive psychotherapy for several months.
PROMISING MEDICAL ADVANCES
Soaking Up Toxic Protein to Stop Alzheimer's Disease
Scientists used a variant version of a protein called sLRP to soak up a toxic protein from the bloodstream and prevent its buildup in the brains of mice. The toxic protein, called amyloid-beta, forms dense deposits in the brain called plaques that have been linked to the symptoms of Alzheimer's disease. The NIH-funded researchers studied a strain of mice known to develop Alzheimer-like symptoms. Mice treated with the sLRP variant protein had improved learning and memory, and amyloid-beta plaques in their brains were reduced by about 90%.
Stem Cell Treatment Repairs Damaged Rat Hearts
NIH-funded researchers developed a procedure for repairing damaged rat hearts by using cells generated in a dish from human embryonic stem cells. When the human-derived cells were implanted into the damaged hearts of rats, new heart muscle was incorporated into the heart tissue within a month. Further testing showed that the treatment thickened the heart's walls and improved their ability to contract. The accomplishment brings scientists a step closer to a treatment for people who have had heart attacks.
INSIGHTS FROM THE LAB
Versatile Human Stem Cells Created Without Embryos
By modifying only 4 genes in human skin cells, NIH-supported researchers found that they could "reprogram" the cells to give them the characteristics of embryonic stem cells. This major advance could open doors to innovative therapies in the future, where people's own cells might be reprogrammed and used to repair their damaged tissues and organs. The breakthrough might also eventually put to rest the ethical controversy surrounding stem cells.
Genetically Altered Mice See a More Colorful World
By giving mice the gene that allows people to see red hues, scientists created rodents that can see a wider range of colors. Mouse eyes normally have only 2 types of light-detecting photoreceptors, sensitive to blue and green light. NIH-funded scientists created genetically engineered mice that also had photoreceptors for red light, which are found in most primates. Tests showed that the altered mice could perceive different colors better than normal mice. The study suggests that the brains of mammals can quickly adapt to new sensory information. It also provides clues to the evolution of color vision.
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.
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 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.
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.
DISEASE PREVENTION, DIAGNOSIS, AND TREATMENT
Study Shows Diuretics Work Better than Newer Medicines for High Blood Pressure — The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a long-term, multi-center trial of antihypertensive therapies funded by NIH, found that diuretics work better than newer therapies in treating high blood pressure and reducing the risk of heart disease in both black and non-black patients. The large study, with 33,357 participants, concluded that diuretics should be the first therapy for most patients with high blood pressure.
Rapid New Test Developed for Inherited Immune Deficiency — NIH researchers developed a new laboratory method that rapidly identifies babies born with inherited forms of Severe Combined Immunodeficiency (SCID), an illness in which the infant fails to develop a normal immune system. SCID babies can be infected by a wide range of viruses, bacteria and fungi that are normally controlled by a healthy baby's immune system. If undetected and untreated, SCID typically leads to death before the baby's first birthday. The new genetic test, which still must be validated before widespread use, could someday be added to the panel of tests that already screen newborns for a variety of disorders.
GENOMICS AND GENETICS
Dog Genome Sequence Published — An international team supported by NIH published the genome sequence of the dog. Because of selective breeding over the past few centuries, modern dog breeds are a model of genetic diversity, from 6-pound Chihuahuas to 120-pound Great Danes, from high-energy Jack Russell Terriers to mild-mannered basset hounds, and from the herding instincts of Shetland sheepdogs to pointers pointing. However, selective breeding has also caused many dog breeds to be predisposed to genetic disorders including heart disease, cancer and blindness. In combination with the human genome, the dog genome sequence will help researchers identify genetic contributors to several diseases.
Research Sheds New Light on Role of Sex Chromosomes in Health and Disease — Two studies provided a detailed analysis of the X chromosome's DNA sequence and a survey of its gene activity. This first comprehensive analysis of the sequence of the human X chromosome, supported by NIH as well as by the Department of Energy, provides new insights into the evolution of sex chromosomes and the biological differences between males and females. Even though it contains only 4% of all human genes, the X chromosome accounts for almost 10% of inherited diseases caused by a single gene, including red-green color blindness, hemophilia, some forms of mental retardation and Duchenne muscular dystrophy. More than 300 diseases have already been linked to it.
NEW RESEARCH DIRECTIONS
Protein Structure Initiative Advances to Rapid Production Phase — The Protein Structure Initiative (PSI) completed its first 5-year phase and moved into its second. The PSI, which is funded largely by NIH, aims to figure out the three-dimensional shapes of proteins, with the long-term goal of being able to predict most protein structures from their DNA sequences. More than 1,100 protein structures were solved in the PSI's first phase, which was dedicated to figuring out how to process proteins and determine their three-dimensional structures more efficiently. Phase 2 is the production phase, in which thousands more protein structures will be solved and put into the Protein Data Bank (http://www.rcsb.org/pdb/), a public repository with powerful tools for processing protein structure information.
Gene Therapy Restores Hair Cells and Improves Hearing in Deaf Guinea Pigs — Researchers supported by NIH successfully used gene therapy to grow new hair cells and restore some hearing in deaf guinea pigs. The scientists used a harmless virus to insert a gene called Atoh1, a key regulator of hair cell development, into cells in the inner ears of deaf adult guinea pigs. Eight weeks after treatment, new hair cells had grown in the ears treated with Atoh1, and their hearing had improved. This is the first time that researchers have restored auditory hair cells in live adult mammals. The researchers caution that it will be several years before Atoh1 gene therapy will be ready to test in humans. Nevertheless, this study is an important advance in hearing research. Scientists are now one step further in the search for new ways to treat hearing loss, a condition affecting about 28 million Americans.
DISEASE PREVENTION, DIAGNOSIS AND TREATMENT
New Treatment Improves Outlook for Breast Cancer Survivors — An international clinical trial supported in part by NIH concluded that women should consider taking letrozole after five years of tamoxifen treatment to continue to reduce the risk of breast cancer recurrence. This very important advance in breast cancer treatment will improve the outlook for many thousands of women.
Gene Mutation Linked to Drug Effectiveness in Lung Cancer — Mutation of a gene involved in non-small cell lung cancer determines whether the drug gefitinib (Iressa™) will cause the tumors to shrink. Gefitinib is one of a new generation of cancer chemotherapy drugs designed to target specific molecular defects that cause cancer. Previously, gefitinib had been shown to cause tumor regression in certain patients but not others, and researchers hadn’t been able to predict which ones would respond. The mutation, discovered by a team that included NIH researchers, is in a gene that codes for the epidermal growth factor (EGF) receptor – the enzyme through which EGF sparks cell growth. Inhibition of this type of enzyme has recently been a focus for cancer researchers, but gefitinib had not been as effective as some had expected based on earlier clinical trials conducted in Japan. With this new discovery, doctors will be able to select those lung cancer patients who could benefit from gefitinib.
Molecular Test Can Predict Risk of Breast Cancer Recurrence — A new test can predict the risk of breast cancer recurrence and may help identify women who will benefit most from chemotherapy, according to research supported by NIH. The researchers used tissue samples and medical records from women enrolled in clinical trials of the cancer drug tamoxifen, which blocks the effect of estrogen on breast cancer cells. These women had a kind of breast cancer called estrogen receptor-positive, lymph node-negative (which means it needs estrogen to grow but has not spread to the lymph nodes). Using samples from 447 patients and a collection of 250 genes, the researchers created a formula that can measure the risk that a given cancer will recur. Their results suggest that almost half of the 43,000 US women that are diagnosed with estrogen-dependent, lymph-node negative breast cancer every year may not need to go through the discomfort and side effects of chemotherapy.
Estrogen and Heart Disease — NIH instructed participants in the estrogen-alone study of the Women’s Health Initiative (WHI), a large multi-center trial, to stop taking their study pills and to begin the follow-up phase of the study. After careful consideration of the data, NIH concluded that with an average of nearly 7 years of follow-up completed, estrogen alone does not appear to affect (either increase or decrease) heart disease, a key question of the study. At the same time, estrogen alone appears to increase the risk of stroke and decrease the risk of hip fracture. It has not increased the risk of breast cancer during the time period of the study. The increased risk of stroke in the estrogen-alone study is similar to what was found in the WHI study of estrogen plus progestin when that trial was stopped in July 2002. The NIH believes that an increased risk of stroke is not acceptable in healthy women in a research study.
Rotavirus Vaccine Created by NIH Scientists Licensed for Commercialization — An effective oral rotavirus vaccine created by NIH scientists in the 1980s and developed further through a cooperative research and development agreement with an industry partner has now been licensed by the NIH Office of Technology Transfer to BIOVIRx, Inc. This vaccine can help prevent the hundreds of thousands of deaths annually from rotavirus diarrhea in children living in developing countries.
Effectiveness of Safer Smallpox Vaccine Demonstrated Against Monkeypox — A mild, experimental smallpox vaccine known as modified vaccinia Ankara (MVA) is nearly as effective as the standard smallpox vaccine in protecting monkeys against monkeypox, a study by NIH researchers found. Monkeypox is used to test the effectiveness of a smallpox vaccine because of its similarity to the smallpox virus. These findings are important in the search for a replacement vaccine for people with health conditions that would prevent them from using the current smallpox vaccine.
Mutant Gene Linked to Treatment-Resistant Depression — A mutant gene that starves the brain of serotonin, a mood-regulating chemical messenger, has been discovered and found to be ten times more prevalent in depressed patients, researchers funded by NIH have found. The gene codes for the brain enzyme tryptophan hydroxylase-2, which makes serotonin. The mutant version results in 80 percent less of the neurotransmitter. It was carried by nine of 87 depressed patients, three of 219 healthy controls and none of 60 bipolar disorder patients. Patients with the mutation failed to respond well to the most commonly prescribed class of antidepressant medications, which work via serotonin, suggesting that the mutation may underlie a treatment-resistant version of the illness.
Combination Treatment Most Effective in Adolescents with Depression — A clinical trial of 439 adolescents with major depression found a combination of medication and psychotherapy to be the most effective treatment. Funded by the NIH, the study compared cognitive-behavioral therapy (CBT) with fluoxetine, currently the only antidepressant approved by the Food and Drug Administration for use in children and adolescents. Seventy-one percent of participants responded to the combination of fluoxetine and CBT.
Researchers Report Early Success Using Saliva to Detect Oral Cancer — Scientists funded by NIH took a major step forward in using saliva to detect oral cancer. The scientists found that they could measure for elevated levels of four distinct cancer-associated molecules in saliva and distinguish with 91 percent accuracy between healthy people and those diagnosed with oral squamous cell carcinoma. This so-called "proof-of-principle" study marks the first report in the scientific literature that distinct patterns of "messenger RNA" not only are measurable in saliva but can indicate a developing tumor. Messenger RNA (mRNA) is the molecular intermediate between gene and protein, using the information in a gene to guide how a protein is made. With further refinement of this test, the researchers hope to attain the necessary 99 to 100 percent accuracy of commercial diagnostic tests. Oral squamous cell carcinoma is the sixth most common cancer in the US. Currently, no biochemical or genetic diagnostic tests are commercially available for oral cancer.
Crohn's Disease Treatment Shows Promise in Clinical Trial — In a small, initial clinical trial led by NIH researchers, doctors found that up to 75 percent of people with Crohn's disease responded to an experimental new treatment and up to 50 percent had long-term remission of symptoms. Crohn's, which affects an estimated 500,000 Americans, is an autoimmune disease that attacks the bowels, causing abdominal pain, cramping, diarrhea and rectal bleeding. In severe cases, damaged bowel sections have to be surgically removed. The new treatment is an antibody designed to disable interleukin-12 (IL-12), an immune system protein involved in inflammation. People with Crohn's produce excess IL-12.
Substances Found in Blood May Predict Development of Preeclampsia — Abnormal levels of two molecules found in the blood appear to predict the development of preeclampsia, a life-threatening complication of pregnancy, according to a study by a team that included NIH researchers. Pregnant women with preeclampsia can develop dangerously high blood pressure and begin excreting protein in the urine. In some cases, the condition may progress to eclampsia, a series of potentially fatal seizures. Being able to predict the development of preeclampsia may enable doctors to treat the condition before it becomes a serious problem.
"Care Managers" Help Depressed Elderly Reduce Suicidal Thoughts — An intervention that includes staffing doctors’ offices with depression care managers helps depressed elderly patients reduce suicidal thoughts, a study funded by NIH found. Older Americans comprise 13 percent of the population but account for 18 percent of all suicides. The major risk factor for suicide in late life is major depression. Since most older Americans who kill themselves have seen their doctor within the previous month, treating depression in primary care can be an effective way to save lives.
Methamphetamine Withdrawal and Brain Changes — NIH researchers were part of a team that used PET (positron emission tomography) scans to find that people who have recently stopped abusing the powerfully addictive drug methamphetamine may have brain abnormalities similar to those seen in people with mood disorders. The findings suggest that health workers might improve success rates for methamphetamine users receiving addiction treatment by also providing therapy for depression and anxiety.
Emotion-Regulating Protein Lacking in Panic Disorder — Three brain areas of panic disorder patients are lacking in a key component of a chemical messenger system that regulates emotion, researchers at NIH discovered. The scientists used PET (positron emission tomography) scans to visualize a type of serotonin receptor called the serotonin 5-HT1A receptor, and compared the brains of people who suffered from panic disorder to those who did not. A new radioactive tracer developed by NIH Clinical Center PET scan scientists binds to the receptors, revealing their locations and a numerical count by brain region. In the panic disorder patients, the receptor is reduced by nearly a third in three structures straddling the center of the brain. This finding is the first in living humans to show that 5-HT1A, which is pivotal to the action of widely prescribed anti-anxiety medications, may be abnormal in panic disorder patients.
GENOMICS AND GENETICS
Sequencing Consortium Reports Finished Human Genome Sequence — The International Human Genome Sequencing Consortium, led in the United States by NIH's National Human Genome Research Institute (NHGRI) and the Department of Energy (DOE), published its scientific description of the finished human genome sequence, reducing the estimated number of human protein-coding genes from 35,000 to only 20,000-25,000, a surprisingly low number for our species.
Scientists Compare Rat Genome With Human, Mouse — An international research team supported by NIH completed a high-quality draft sequence of the genome of the laboratory rat, and used that data to explore how the rat's genetic blueprint stacks up against those of mice and humans. The rat sequence draft represents the third mammalian genome to be sequenced to high quality and described in a major scientific publication. Comparing the human genome with those of other organisms is helping researchers to better understand the complex genomic components involved in human health and disease.
Researchers Compare Chicken and Human Genomes — An international research consortium supported by NIH has found that chickens and humans share more than half of their genes, but that their DNA sequences diverge in ways that may explain some of the important differences between birds and mammals. The International Chicken Genome Sequencing Consortium analyzed the sequence of the Red Jungle Fowl (Gallus gallus), which is the progenitor of domestic chickens. The chicken is the first bird, as well as the first agricultural animal, to have its genome sequenced and analyzed. Recent outbreaks of avian flu have highlighted the importance of learning more about the chicken genome.
Gene Variants May Increase Susceptibility to Type 2 Diabetes — International research teams that included several NIH researchers found variants in a gene called hepatocyte nuclear factor 4 alpha (HNF4A) that may predispose people to type 2 diabetes, the most common form of the disease. For years, scientists have known that single-gene mutations contribute to rare forms of diabetes that account for about 2 to 3 percent of all diabetes cases, but type 2 diabetes, which accounts for 90 to 95 percent of all diabetes cases in the U.S., is caused by more than a problem with one gene. Type 2 diabetes usually begins after age 40 in overweight, inactive people and is more common in those with a family history of diabetes. In the United States, type 2 diabetes disproportionately affects African Americans, Hispanic/Latino Americans, and American Indians. Finding a gene that may increase susceptibility to type 2 diabetes is a major breakthrough, but translating this discovery into a treatment that benefits people with diabetes or those at risk is still years away. Scientists need to learn much more about this gene.
Genome Sequence Reveals Leaner, Meaner Intestinal Parasite — Researchers supported by NIH completed the genome sequence of Cryptosporidium parvum, an insidious, one-celled, waterborne parasite that lodges in the intestines of infected people and animals, and for which there is currently no effective treatment. Cryptosporidium is an extremely hardy parasite found in water supplies throughout the world, including the United States. For people with weakened immune systems such as those with HIV/AIDS, the parasite can lead to serious or life-threatening illness. Cryptosporidium has been difficult to study up until now because it has been virtually impossible to grow in the laboratory. With a better understanding of this parasite’s biology, researchers will be better positioned to find treatments that zero in on unique biological processes essential for the organism's survival.
Gene Involved in Juvenile Rheumatoid Arthritis — A genetic variation within the interleukin-6 (IL-6) gene increases susceptibility to systemic juvenile rheumatoid arthritis (JRA), according to researchers funded by NIH and the Arthritis Research Campaign. Juvenile rheumatoid arthritis, which has three main forms, affects each child differently. Some experience swollen, painful or stiff joints. Other common symptoms include skin rashes, weak muscles, fevers and swollen glands. Systemic juvenile rheumatoid arthritis, the most severe type, can also affect internal organs such as the heart, liver, spleen and lymph nodes. Twenty percent of children with JRA have the systemic form. Scientists suspect that JRA is caused by a combination of environmental and genetic factors.
Genes That Determine How Pollution Affects Allergies — Researchers funded by NIH identified a set of genes that influences how pollution affects allergies. People with certain versions of the genes were more likely to have an allergic reaction to ragweed when it was mixed with diesel exhaust particles. These genes code for antioxidant proteins in the lungs that the scientists believe detoxify chemicals found in diesel exhaust particles. This discovery may help scientists identify people whose asthma and hay fever are more affected by pollution. It might also help accelerate the development of drugs to treat and prevent these disorders.
Honey Bee Genome Assembled — The first draft version of the honey bee genome sequence has been deposited into free public databases. The sequence of the honey bee, Apis mellifera, was funded largely by NIH, along with the U.S. Department of Agriculture. The honey bee is valued by farmers for its ability to produce honey and pollinate crops. Biologists also are interested in the honey bee's social instincts and behavioral traits.
NEW RESEARCH DIRECTIONS
Sperm Provides Target for New Contraceptive Approach — A team of researchers funded by NIH found an enzyme in sperm that is necessary for sperm movement. Mice bred to lack this enzyme produce sperm that cannot swim toward egg cells to fertilize them. The enzyme, known as GAPDS, is essentially the same as an enzyme produced in human sperm. It is found in the sperm's flagellum, the snake-like tail which whips back and forth to propel the sperm forward. Researchers believe that designing a drug to disable this enzyme might provide the basis for an effective new form of male contraception. An understanding of the enzyme and related chemical reactions might also lead to insights into treatment for some forms of male infertility.
Researchers Identify Brain Protein that Halts Progression of Alzheimer's — Researchers funded by NIH have identified a protein in the brain that halts the progression of Alzheimer's disease in human brain tissue. The protein, known as transthyretin, protects brain cells from gradual deterioration by blocking another toxic protein that contributes to the disease. Scientists are hopeful that this research will inspire a new approach to the treatment of Alzheimer's, one focused on preventing the loss of the brain cells instead of treating the resulting symptoms. More studies are needed to understand how transthyretin might be used in treating Alzheimer's patients.
Scientists Take 'Snapshot' of Molecular Tether for Anthrax and Staph Bacteria — Scientists funded by NIH have snapped a picture of the molecular tether that anthrax- and staph-causing bacteria use to hook onto human red blood cells. The tether, an enzyme called sortase B, allows the bacteria to rob the cells of iron, which they need to survive. Anthrax infection can be life-threatening, while staph is responsible for a range of health problems, including skin infections and food poisoning. The scientists hope to use their knowledge of this enzyme's structure to rationally design new antibiotics that would nip dangerous bacteria in the bud, before they have a chance to cause infections.
Researchers Find Protein That Makes Long-Term Memory Possible — From language to literature, from music to mathematics, a single protein, known as mBDNF, appears central to the formation of the long-term memories needed to learn these and all other disciplines. This discovery brings the possibility of studying this protein system in people with learning and memory disorders and perhaps designing new medications to help compensate for these problems.
Brain Signal Predicts Working Memory Prowess — A person’s capacity for visual working memory can be predicted by his or her brain waves, researchers funded by NIH discovered. Some people are better than others at remembering what they have just seen — holding mental pictures in mind from moment to moment. The researchers found that a key brain electrical signal leveled off when the number of objects held in a person’s mind exceeded their capacity to accurately remember them, while it continued to soar in those with higher capacity.
New Technique Helps Scientists Solve 3-D Protein Structures — A new technique for engineering protein crystals is helping scientists figure out the three-dimensional structures of some important biological molecules, including a key plague protein whose structure has previously eluded researchers. The “crystal engineering” technique, developed with support from NIH, promises to help pharmaceutical companies develop more effective drugs to treat various diseases by tailor-making molecules to "fit" a protein's shape.
New Eggs Continue to Develop in Adult Mice — Contrary to long-held scientific views that the number of oocytes (eggs) in the ovaries of most mammals is fixed at birth, scientists supported by NIH reported that new oocyte-containing follicles continue to develop in the ovaries of adult mice. The research suggests that these new oocytes come from stem cells located in the ovary. Scientists have long believed that no new oocytes were made after the ovary of any mammal, including a woman, was formed, but this study provides evidence challenging this belief.
HIV-Blocking Protein in Monkeys — Scientists funded by NIH identified a protein that blocks HIV replication in monkey cells. Humans have a similar protein, although it is not as effective at stopping HIV. The protein, called TRIM5-alpha, blocks a key early stage of HIV infection: the removal, or uncoating, of the protective shell surrounding HIV’s genetic material. This coat, called the capsid, must be removed before HIV can insert its genetic material into the host cell’s DNA and begin to make copies of itself. The identification of a specific protein that powerfully inhibits viral uncoating provides a scientific springboard for future HIV/AIDS therapies.
Monkey Talk, Human Speech Share Left-Brain Processing — NIH researchers were part of a team that used PET (positron emission tomography) to pinpoint circuits in the monkey brain that could be precursors of those in humans for speech and language. As in humans, an area specialized for processing species-specific vocalizations is on the left side of the brain. An area near the left temple responded significantly more than the same area on the right to monkey calls, but not to other animal calls, human voices or various other sounds.
Transgenic Animals Produced Using Cultured Sperm — NIH researchers, in collaboration with Japanese colleagues, successfully created transgenic zebrafish – ones to which novel genes have been added – using sperm cells grown under laboratory, or in vitro, conditions. This is the first time that sperm cells have been cultured entirely in vitro and used to produce a transgenic animal. This achievement has implications for a wide range of research from developmental biology to gene therapy. The new technique has the potential to speed the production of many different types of transgenic animals that can shed new light on human development and disease.
Human Genome Project Completed — The International Human Genome Sequencing Consortium, led in the United States by NIH, completed the Human Genome Project more than 2 years ahead of schedule and for a cost substantially less than the original estimates. The international effort to sequence the 3 billion DNA letters is considered by many to be one of the most ambitious scientific undertakings of all time. The first draft of the human sequence was completed in June 2000. Since then, researchers have worked to convert the "draft" sequence into a "finished" sequence, which covers about 99 percent of the human genome's gene-containing regions, and has been sequenced to an accuracy of 99.99 percent. All of the sequence data have been deposited into public databases and made freely available to scientists around the world, with no restrictions on their use or redistribution.
Protein From Algae Inhibits Ebola — A bacterial protein known to reduce the ability of the human immunodeficiency virus (HIV) to infect cells was also found to inhibit the Ebola virus. The protein, cyanovirin-N, is found in blue-green algae. An NIH-led team found that the protein inhibits Ebola infection by interfering with the virus's ability to enter cells, and can extend the survival of Ebola-infected mice. This study provides important insights that may help in the development of medicines to combat Ebola infection, which causes severe hemorrhagic fever and has a high mortality rate.
Mouse Genome Sequenced - The international Mouse Genome Sequencing Consortium, jointly funded by several NIH Institutes along with the Wellcome Trust, published a high quality draft sequence of the mouse genome - the genetic blueprint of a mouse - together with a comparative analysis of the mouse and human genomes. This is the first time scientists have compared the human genome with another mammal's. Because the mouse carries a very similar set of genes, this information will allow scientists to learn more about human genes and the proteins they encode, leading to a better understanding of human disease and improved treatments and cures. The sequence is posted on the Internet, where it is freely available.
Help for Urinary Incontinence - Researchers supported by NIH showed that rural older women with urinary incontinence (UI) who received a behavioral management intervention in their homes reduced UI severity by 61% compared to the control group, whose UI severity increased by 184%. The intervention consisted of behavioral changes, bladder training, and pelvic muscle exercises with biofeedback. UI is a leading reason for people in rural areas to move to a nursing home; controlling it would lead to a better quality of life and allow people to remain longer in their homes.
DASH (Dietary Approaches to Stop Hypertension) Diet Lowered Blood Pressure found that the DASH (Dietary Approaches to Stop Hypertension) diet combined with reduced intake of sodium lowered blood pressure for all groups of people, not just those with high blood pressure. The diet is rich in fruits, vegetables and low-fat dairy foods but low in fats, cholesterol and sweets. Middle-aged Americans face a 90 percent chance of developing high blood pressure at some time during the rest of their lives, according to NIH's National Heart, Lung and Blood Institute (NHLBI). The condition can lead to stroke, heart disease and kidney failure. (Intramural and Extramural)
Rhesus Monkey Genetically Modified – successfully introduced a new gene into rhesus monkeys. This is the first time that a primate, the group of mammals that includes human beings, has been genetically modified. The accomplishment could lead to the development of new, more relevant animal models that provide insights into a variety of human disorders, including cancer, cystic fibrosis and Alzheimer's disease. (Extramural)
Working Draft of the Human Genome – assembled a working draft of the sequence of the entire human genome, the genetic blueprint for a human being. This draft contains overlapping fragments of DNA sequence–the order of the four chemical bases that make up DNA–covering approximately 90 percent of the genome, with some gaps and ambiguities. Sequence information from this public project has been continuously, immediately and freely available with no restrictions on its use or redistribution. Already, many tens of thousands of genes have been identified and dozens of disease genes pinpointed by access to the working draft. The international Human Genome Sequencing consortium responsible for this working draft includes scientists at 16 institutions in the United States, France, Germany, Japan, China, and Great Britain. The project is funded by grants from government agencies and public charities in these various countries. (Intramural and Extramural)
Oxygen Can Cut the Rate of Wound Infections in Half – demonstrated that a simple and inexpensive change in basic surgical procedures–giving patients more oxygen during and immediately after surgery–can cut the rate of wound infections in half, thus saving millions of dollars in hospital costs by helping to prevent post-surgical wound infection, nausea and vomiting. (Extramural)
Completed Sequence of Human Chromosome 22 – completed first sequence of a human chromosome, chromosome 22. Genes on chromosome 22 have been implicated in immune system function, congenital heart disease, schizophrenia, mental retardation, birth defects, and several cancers, including leukemia. The 33.4 million nucleotides that make up chromosome 22 comprise the longest continuous stretch of DNA ever deciphered. (Extramural)
Overwhelming Success in Treatment for Sickle Cell Anemia – a clinical trial of treatment for sickle cell anemia was halted early due to its overwhelming success. Daily administration of the drug hydroxyurea reduced the frequency of painful episodes and related hospital visits by about 50%; reduced the frequency of acute chest syndrome, a life-threatening complication of sickle cell anemia characterized by chest pain, fever, prostration, and an abnormal chest X-ray; and reduced the number of blood transfusions for patients in the study. Sickle cell anemia is an often fatal disease that affects millions throughout the world. Approximately 2 million Americans carry the sickle cell trait, and about 72,000 are affected by the disease. (Intramural and Extramural)
Two Breast Cancer Susceptibility Genes Indentified – identified two breast cancer susceptibility genes, BRCA1 and BRCA2, that together account for up to 70% of all hereditary breast cancers (between 5% and 10% of all breast cancer is hereditary). Mutations in BRCA1 and BRCA2 have also been implicated in ovarian cancers, and BRCA2 mutations have now been associated with increased risks of cancers of the prostate, pancreas, gallbladder, bile duct, and stomach as well as malignant melanoma. (Extramural and Intramural)
CMV Retinitis Treatment – improved treatment for CMV retinitis, a potentially blinding retinal disease that affects about one of every four people with AIDS. (Intramural and extramural)
Gene Tranfer in Humans – first transfer of a foreign gene into humans. (Intramural)
Therapy for Protecting the Vision of Premature Infants – showed that briefly freezing the outer part of the retina with a probe can protect the vision of many premature infants with retinopathy of prematurity. This research could save the Federal government as much as $20 million annually. (Extramural)
Genetic Origin of Cancer – discovered that oncogenes have normal cellular functions, thus laying the cornerstone for understanding the genetic origin of cancer and widening the insight into the complicated signal systems that govern the normal growth of cells. (Extramural; Nobel prize in 1989)
Laser Surgery an Effective Treatment for Diabetic Retinopathy – established laser surgery as a safe and effective treatment for diabetic retinopathy. It is estimated that laser surgery for this disease will save the Federal government up to $2.8 million over the next 20 years. (Extramural)
Demonstrated Laboratory Protein Synthesis – demonstrated that the information required to fold the polypeptide chain of ribonuclease into the specific three-dimensional form of the active enzyme resides in the sequence of amino acids. Thus it became clear that this protein could be synthesized in the laboratory by joining the proper amino acids in the correct order and allowing the chain of amino acids to spontaneously fold. (Intramural; Nobel prize in 1972)
Effectiveness of Neonatal Screening for PKU – documented the effectiveness of neonatal screening and dietary restriction in preventing mental retardation due to phenylketonuria. (Extramural)
– first complete removal and successful replacement of a patient's diseased mitral valve with an artificial one, which was developed at NIH. (Intramural)
– discovered that low levels of fluoride in drinking water could prevent tooth decay. This work began in the 1930s, continued through the 1940s and culminated in the 1950s. (Intramural)
The list of NIH research advances, 1887-1950, was compiled by Victoria A. Harden and Harriet Greenwald. Selected portions were published as "Timeline of NIH Discoveries, 1887-1929," in NIH Alumni Association newsletter, Update 2 (Winter 1990): 8-11; and "Timeline of NIH Discoveries, 1930-1940," in ibid. 4 (Winter 1992): 9-11.For further information email: firstname.lastname@example.org
1887 Laboratory of Hygiene founded. Director Joseph J. Kinyoun made the first laboratory diagnosis of cholera in the western hemisphere.