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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 thus far this year.

Year 2004

Disease Prevention, Diagnosis, and Treatment

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.
   
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.
   
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.
   
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

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.
   
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.
   
Chicken Genome Assembled — The first draft of the chicken genome sequence has been deposited into free public databases for use by biomedical and agricultural researchers around the globe. Researchers supported by NIH successfully assembled the genome of the Red Jungle Fowl, Gallus gallus, which is the ancestor of domestic chickens. Comprised of about 1 billion DNA base pairs, the chicken genome is the first avian genome to be sequenced. Recent outbreaks of avian flu have highlighted the importance of learning more about the chicken genome and how genetic variation may play a role in the susceptibility of different strains to the disease.
   
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

Brain Signal Predicts Working Memory Prowess — A person’s capacity for visual working memory can be predicted by his or her brainwaves, 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.
   

Prepared by Harrison Wein, Ph.D.
Email: weinh@od.nih.gov
May 4, 2004

 

This page was last reviewed on October 27, 2004 .

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