Biomedical Research at the National Institutes of Health

• Conducting research in its own laboratories
• Supporting the research of scientists in universities, medical schools, hospitals, and research institutions in the United States and throughout the world
• Training research investigators
• Promoting the communication of medical information and research findings

NIH accomplishes its mission by conducting and funding both basic and clinical research. Basic research involves the fundamental studies of molecules, genes, proteins, cells, tissues, and organisms that lead to a better understanding of the workings of our natural world. Basic research may not have an immediate payoff, but it can help us understand the underlying principles of how biological systems function. This sets the stage for later medical advances that depend on this basic understanding of biology. Clinical research focuses on developing and testing new approaches to the prevention, diagnosis, and treatment of disease. Together, basic and clinical research are our most powerful weapons against disease and disability.

Approximately 10 percent of the NIH budget funds research conducted through the NIH Intramural Research Program. The intramural program supports more than 2,000 research projects conducted by more than 4,000 doctoral-level scientists at NIH. NIH’s main campus is located in Bethesda, Maryland. The intramural program also has laboratories at other locations in Maryland (Frederick and Baltimore) and in other States, including the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina; the National Institute of Diabetes and Digestive and Kidney Diseases’ Epidemiology and Clinical Research Branch in Phoenix, Arizona; and the National Institute of Allergy and Infectious Diseases’ Rocky Mountain Research Station in Hamilton, Montana.

The bulk of the NIH budget, approximately 82 percent, is invested in the extramural program, which supports research through grants and contracts at more than 2,000 research institutions throughout the United States and abroad.

The rewards of this investment have come in the form of scores of scientific discoveries that are already helping researchers and physicians better understand, prevent, and treat cancer, diabetes, heart disease, and neurological disorders, as well as AIDS and other infectious diseases. A small sampling of some of the research advances made in recent years through the intramural program, the extramural program, and collaborative efforts is outlined below.

Recent Major Advances	Return to Top

Human Genome

In February 2001, scientists throughout the world achieved a monumental milestone: they sequenced nearly all of the 3 billion or so base pairs that make up the human genome, the DNA contained in all the human chromosomes in each cell of the human body. This feat was achieved through the Human Genome Project, an international consortium of scientists from the United States, England, Japan, Germany, France, and China. The researchers published a draft sequence of the human genome that represents an exact order of four nucleotide bases that comprise the base pairs within DNA. The draft sequence represents more than 90 percent of the total human DNA sequence.

In addition to determining the sequence of the human genome, the international consortium published a nearly complete physical map of the human genome. The sequence reveals the order of bases along a DNA strand, whereas the genome map shows the position of the genes within the genome. The project turned up a few surprises. For example, scientists found that the human genome contains far fewer genes than previously predicted. Instead of the 100,000 genes thought to exist, the human genome contains only about 35,000 genes. Researchers also found that the human genome contains much more “junk” than previously realized. About half of the genome consists of stretches of DNA that do not code for any proteins.

The findings are already changing the face of genetics throughout the world. For example, tens of thousands of new genes have been identified from the human genome sequence, including more than 30 genes that play a role in human disease. Scientists are also using the information to examine patterns of genes expressed under certain conditions, such as cancer.

With research contributions from both extramural and intramural scientists, the Human Genome Project, which was funded in large part by NIH, completed the sequence and mapping of the entire human genome in 2003.

Cancer	Return to Top

DNA Microarray Technology
Physicians treating cancer patients have long been baffled by a mystery of sorts. Among patients who seem to have similar symptoms with the same type and stage of cancer, some respond to standard therapies and are cured, while others fail to respond and die. But new research reveals that cancer cells that appear similar through a microscope may be quite different on a molecular level.

Researchers at NIH and their collaborators have recently developed a powerful technique that can distinguish between different types of closely related cancers. The technique, known as DNA microarray technology, anchors thousands of specific, known DNA sequences to a grid on a silicon microchip. Researchers can then bind complementary sequences of unknown genes that are expressed in a cell or tissue to evaluate the pattern of gene expression from a patient’s cells. Different subtypes of cancers can have different patterns of gene activation that are characteristic of that cancer subtype.

Understanding these subtle differences may help physicians develop better ways to understand, prevent, and treat different cancers.

Breast Cancer
Physicians treating patients with breast cancer have long sought a better way of distinguishing hereditary forms of breast cancer from sporadic forms of the disease. Approximately 5 percent of women with breast cancer inherit genetic mutations that predispose them to the disease, whereas women with sporadic breast cancer accumulate genetic changes over time that can eventually lead to cancer. Hereditary breast cancers are often more aggressive, affect women at younger ages, and may require a different course of treatment. Over the past decade researchers discovered that mutations in two genes, BRCA1 and BRCA2, give rise to most cases of hereditary breast cancer. However, the genes are very large, and it is difficult to pinpoint the genetic mutations that are triggering disease.

Researchers at NIH’s National Human Genome Research Institute turned to DNA microarray technology to see if different types of breast cancer cells express different patterns of genes. The researchers analyzed the expression of more than 6,000 genes from breast cancer cells and found clear differences between hereditary and nonhereditary breast tumors. The researchers found that the pattern of genes activated was different among tumors with BRCA1, BRCA2, and sporadic mutations. The researchers distinguished the three categories of tumors by analyzing 50 or 60 specific genes. Understanding how the activation of these subsets of genes results in different paths of cancer development may help researchers develop new targets for treating and preventing breast cancer.

Childhood Cancers
Physicians also have difficulty distinguishing four types of closely related childhood cancers: neuroblastoma, rhabdomyosarcoma, non-Hodgkin’s lymphoma, and Ewing’s sarcoma. Under the microscope, cells from these four cancers appear very similar and are difficult to differentiate. Because of their similarity, these cancers are sometimes misdiagnosed and not treated appropriately.

Researchers at NIH collaborated with investigators in Sweden to study these cancer cells using DNA microarray technology. They were able to distinguish the cancers from each other by analyzing the expression of a set of 93 genes. Forty-one of these genes were not previously known to be involved in the development of the cancers. The researchers hope that studying these genes will help them better understand the biology of these cancers and possibly serve as targets for developing new cancer drugs.

Ovarian Cancer
Early detection is a critical concern for treating women with ovarian cancer. More than 80 percent of patients are not diagnosed until the cancer has progressed to later stages when they have a less than 20 percent chance of surviving for 5 years. In contrast, patients who are diagnosed at early stages have a 95 percent survival rate at 5 years.

NIH researchers and their collaborators have developed a new test that can detect ovarian cancer, even at early stages. The scientists combined another cutting edge technology called proteomics with sophisticated artificial intelligence computer programs. Whereas gene chip technology assesses gene expression in cells, proteomics examines cells for the presence of particular proteins. The scientists used computers to study the patterns of proteins present in samples from known cancer patients, then looked for these same patterns in unknown samples. The test was able to correctly identify all samples from patients with stage I ovarian cancer.

The proteomics test can be used to detect ovarian cancer and potentially other cancers as well, using a blood sample from a finger-prick. Researchers believe the technology will go a long way toward helping women combat this devastating disease.

Prostate Cancer Gene Discovered
Approximately 16 percent of American men will develop prostate cancer sometime in their life. Scientists have been searching for the genetic mutations that cause prostate cancer for several decades. This year, researchers at NIH and their collaborators discovered a new gene on chromosome 1 linked with an inherited form of prostate cancer. The gene, which codes for a protein called ribonuclease L (RNASEL), is mutated in some families with a history of prostate cancer. The RNASEL protein plays a role in targeting damaged or abnormal cells for programmed cell death. The mutated cells may become cancerous when this normal way of ridding the body of damaged cells is inactivated. RNASEL is probably just one of several proteins that contribute to prostate cancer.

Novel Anticancer Drug Discovered
Until recently most cancer patients have had to endure painful rounds of chemotherapy drugs aimed at killing their cancer cells. The problem with most chemotherapy drugs is that they also kill normal cells and cause debilitating side effects. The strategy has been able to give enough drug to kill the cancer but not enough to kill the patient and hope that the cancer does not recur. For years, researchers have been searching for drugs that will specifically target cancer cells without harming normal cells or the patient.

In May 2001 the FDA approved the use of a member of a new class of anticancer drug, Gleevec, to treat chronic myelogenous leukemia (CML). Gleevec produced dramatic results in an early phase clinical trial, in which normal blood counts were restored in 53 out of 54 patients given the drug.

The drug, developed by the pharmaceutical company Novartis, is the first of a new generation of anticancer drugs that specifically target a protein known to contribute to the development of cancer. CML is caused by the translocation of a piece of chromosome 22, which fuses to chromosome 9. A gene called bcr is broken off of chromosome 22 and fused to a second gene called abl on chromosome 9. This fusion creates a new gene called bcr-abl that codes for a protein that belongs to a class of proteins known as tyrosine kinases. Tyrosine kinases play important roles in regulating cell growth, but bcr-abl causes cells to divide uncontrollably, leading to leukemia. Gleevec specifically blocks the action of the bcr-abl protein in leukemia cells but does not affect normal cells.

In a recently completed Phase II study of Gleevec, designed to test both the safety and the efficacy of the drug, 454 patients with CML who had not responded to standard therapy took Gleevec on a daily basis. After 18 months, 95 percent of the patients were alive and 89 percent were free of disease progression.

NIH has funded much of the basic research that led to the discovery of Gleevec and is continuing to support and coordinate clinical trials of the drug. Currently, clinical trials are being held to test the long-term effects of Gleevec in CML patients, as well as the effect of Gleevec in patients with other types of cancer, including glioblastomas and sarcomas.

AIDS Research	Return to Top

HAART
When AIDS first appeared in this country and throughout the world, the disease was a virtual death sentence. Although there is still no cure, researchers have made great strides in developing treatment regimens to combat the devastating disease. Over the past several years, an AIDS treatment strategy called highly active antiretroviral therapy (HAART) has proven remarkably successful in reducing HIV levels and preventing the progression of AIDS in HIV-infected patients. Many patients have experienced a reduction in HIV to undetectable levels in the blood. However, the therapy, which consists of combinations of three or four potent antiretroviral drugs, can be toxic, difficult to adhere to, and prohibitively expensive.

NIH researchers recently studied the feasibility of cycling on and off these medications. The researchers showed that this approach, called structured intermittent therapy, appeared to effectively control HIV replication while reducing some of the side effects of HAART. The study involved 10 patients who had been receiving daily HAART. During the study, patients received a four-drug regimen of the anti-HIV drugs stavudine, lamivudine, indinavir, and ritonavir, administered twice a day for a period of 7 days, followed by a 7-day period with no drugs. This on-off cycle was repeated 16–34 times, or 32 to 68 weeks. The researchers found that study patients had no significant increases in the amount of HIV in their bodies and no reduction in CD4+T cells, important immune cells that are typically depleted in HIV-infected patients. The researchers also found that patients on structured intermittent therapy had reduced serum cholesterol and triglyceride levels. Typically, HAART therapy increases serum cholesterol and triglyceride levels, which can contribute to heart problems in patients.

The success of the initial pilot study has prompted larger clinical trials of structured intermittent therapy. The researchers hope that the approach could reduce the side effects and high costs of HAART, which have impeded its widespread use, particularly in underdeveloped nations, where more than 95 percent of HIV-infected individuals live.

HIV Vaccine Development
As a result of new scientific findings and new funding in the area of HIV vaccines, many new approaches are being pursued from the basic research level through vaccine product development. In the past several years, investigators have determined that several AIDS vaccine strategies have been able to decrease the level of the virus that was established shortly after challenge in animal models. Even though these vaccines have not been totally effective in preventing virus infection, the concept that control of viral load may be an equally important vaccine outcome has been recognized because of data that suggest that partners of HIV-infected subjects become infected far less frequently when there is a reduced level of HIV transmission.

In November of 2002, NIH’s Vaccine Research Center (VRC) launched a Phase I clinical study of a novel DNA vaccine directed at the three most globally important HIV subtypes, or clades. The vaccine, developed by VRC, incorporates HIV genetic material from clades A, B, and C, which cause about 90 percent of all HIV infections around the world. This is the first multigene, multiclade HIV vaccine to enter human trials and marks an important milestone in the search for a single vaccine that targets U.S. subtypes of HIV as well as clades causing the global epidemic.

Reducing Mother-to-Child Transmission
In 2002 alone, approximately 800,000 children worldwide became infected with HIV through mother-to-child transmission, with more than 90 percent residing in resource-poor countries.

A regimen of the HIV drug AZT, administered to the mother during labor and to the infant during the first week after birth, reduces the infection rate, but AZT is expensive and requires multiple doses due to its short half-life. A recent NIH-funded study by Ugandan and U.S. researchers found that two doses of the inexpensive antiviral drug nevirapine (NVP)—one dose to the mother and one to the child—reduced HIV transmission by 41 percent over infants and mothers who received an AZT regimen. At 18 months, 25.8 percent of children in the AZT group were infected with HIV, compared with 15.7 percent in the NVP group, yielding a difference of 41 percent when a time variable is considered. The cost savings of using nevirapine in the study were substantial—approximately 70 times less than the AZT treatment.

Heart Disease	Return to Top

The scientific mainstream has long believed that certain types of cells, once destroyed, are gone forever. For decades physicians have been telling their patients that heart muscle damaged during a heart attack cannot be repaired or regenerated. But two recent studies now challenge the longstanding dogma.

NIH-funded researchers in collaboration with researchers at NIH in Bethesda discovered that bone marrow cells can develop into cardiomyocytes and replace damaged heart muscle in mice. The researchers induced myocardial infarction, or heart attack, in mice by ligating, or tying off, the left main coronary artery, a major blood vessel to the heart. They then injected bone marrow cells into the wall bordering the damaged heart muscle. The bone marrow cells were selectively enriched for a type of bone marrow progenitor cell with a high capacity to develop into a variety of cell types. The researchers found that the injected cells homed in on the damaged tissue and regenerated new myocardium, which occupied 68 percent of the damaged portion of the heart muscle 9 days after injection. The results indicate that bone marrow progenitor cells can replace dead or damaged myocardial cells with functioning living tissue. The results indicate that the heart is much more resilient than previously realized.

Diabetes	Return to Top

Diabetes Prevention
The Diabetes Prevention Program (DPP), a multicenter study sponsored by NIH and conducted at clinics throughout the country, ended a year early when it showed that lifestyle changes can delay and possibly prevent the onset of type 2 diabetes. Seventeen million people in the United States have diabetes today. Type 2 diabetes, the most common form, occurs mostly in people who are older, overweight, sedentary, and have a family history of diabetes. African Americans, Latinos, and Native Americans have an especially high risk of developing type 2 diabetes. Diabetes greatly increases the risk of heart disease, kidney disease, stroke, eye disease, and nerve damage. In fact, it is the main cause of kidney failure, limb amputation, and new-onset blindness and a main cause of heart disease and stroke.

Diabetes, which is characterized by high blood glucose levels, is usually preceded by prediabetes. People with prediabetes have blood glucose levels that are higher than normal, but not high enough to be considered diabetic. Physicians and researchers have long known that regular exercise and changes in diet can lower blood glucose levels in people with diabetes.

The DPP asked whether modest weight loss achieved with these same lifestyle changes or a glucose-lowering medication could delay or even prevent the onset of diabetes. The researchers randomly assigned 3,234 overweight volunteers with prediabetes to one of three groups:

• Lifestyle modification through diet and exercise, with the aim of reducing weight by 7 percent
• Treatment with the drug metformin (an oral medication used to treat type 2 diabetes)
• A control group receiving a placebo in place of metformin

The results showed that people in the diet and exercise group who lost 5–7 percent of their weight lowered the incidence of diabetes by 58 percent. Metformin reduced the incidence of diabetes by 30 percent. Among volunteers over the age of 60, diet and exercise reduced the incidence of diabetes by 71 percent. In addition to delaying or preventing the onset of diabetes, diet and exercise also restored normal blood glucose levels in many people with prediabetes. The researchers plan to continue to monitor study participants to see whether diabetes can be delayed beyond the 3-year followup period in the study.

Islet Transplantation and Stem Cells
Type 1 diabetes, or juvenile-onset diabetes, results from the loss of the insulin-producing islet cells of the pancreas. For unknown reasons, the body’s immune system destroys its own islet cells and patients are unable to produce insulin. Without insulin, the cells of the body cannot function. Researchers would like to find a way to replace the insulin-producing cells of the pancreas in patients with type 1 diabetes. They are finding new hope in islet transplantation.

Researchers are trying to determine whether the procedure can restore natural insulin production in patients with type 1 diabetes. Despite its promise, however, islet transplantation cannot be adopted for widespread use until two major obstacles are overcome: the severe shortage of donor islets and the need for immunomodulatory drugs that safely prevent rejection.

NIH is addressing the inadequate supply of islets by establishing the Beta Cell Biology Consortium to pursue methods for growing an unlimited quantity of functional insulin-secreting beta cells. Studies on immune tolerance, which would permit transplantation without the need for chronic immunosuppressive drugs, are focusing on the problem of rejection of transplanted tissue. In related work, NIH is funding research resources, such as islet isolation centers, to obtain human islets from donor pancreases for use in islet transplantation studies, as well as research to find ways to prevent the immune system from rejecting the transplanted islets.

Stem cell research may also provide methods for developing a renewable supply of islets. Recently, scientists at NIH induced mouse stem cells to develop into insulin-producing islet clusters similar to those found in the pancreas. The researchers started with embryonic stem cells of mice. The stem cells spontaneously form aggregates called embryoid bodies, which contain all three primordial germ layers. The researchers then selected a subpopulation of cells that express a specific neural marker. After subjecting the cells to a five-stage culturing technique, the cells formed islet-like pancreatic clusters. The cells responded to normal glucose concentrations by secreting insulin and survived when transplanted into mice. Researchers hope that this technique may lead to a way to develop insulin-producing cells for people with type 1 diabetes.

Neurological Disorders	Return to Top

Spinal Cord Injury
Each year, approximately 100,000 Americans suffer an injury to the spinal cord, often causing paralysis, muscle atrophy, breathing difficulties, and chronic pain. An estimated 200,000 individuals in the United States live day-to-day with the devastating consequences of such injuries.

Recently, NIH-supported researchers found that delayed treatment of spinal cord injury may improve recovery. In the study, rats given an experimental combination therapy—consisting of fetal spinal tissue transplants and nerve growth factors (neurotrophins)—several weeks after their spinal cords were severed showed dramatically greater re-growth of nerve fibers and recovery of function than rats treated immediately after injury. The finding suggests that the window of opportunity for treating spinal cord injury may be wider than previously anticipated.

Earlier studies in animals have shown that fetal tissue transplants and neurotrophins can improve regrowth of injured neurons in the adult spinal cord and that some injured neurons can regrow even after long periods of time. However, this study is the first to show that spinal cord regeneration is actually improved when treatment is postponed until most of the initial injury-related changes in the rat spinal cord have taken place and the surrounding environment has stabilized.

Translational Research
The Neurodegeneration Drug Screening Consortium—a novel partnership between the National Institute of Neurological Disorders and Stroke and three voluntary health organizations—was created to identify drugs that may be useful for treating neurodegenerative disorders. Recently, the group met to discuss results of the initial phase of the program—a large-scale, 6-month project in which investigators from 26 laboratories tested 1,040 compounds. They used 29 different assays to identify possible effects of the drugs on cell death, protein aggregation, and other processes linked to neurodegenerative diseases.

Most of the tested compounds had previously been approved by the FDA for use in treating other disorders. FDA-approved drugs generally have advantages over newly identified compounds because they are already on the market and have undergone years of testing in humans. More research is needed before the tested compounds can be considered for clinical trials in patients with neurodegenerative disorders.

Muscular Dystrophy
In a recent NIH-supported study, scientists identified a new kind of genetic problem that underlies a common neuromuscular disorder called facioscapulohumeral muscular dystrophy (FSHD). The study showed that deletion of repetitive DNA sequences in people with FSHD causes overactivity in nearby genes. The finding solves a decades-old mystery about the causes of this disorder and may ultimately lead to the first effective treatments.

The researchers found that abnormally short strings of repeated DNA sequences on chromosome 4 interfere with the function of a protein complex that controls nearby genes, leading to overactivity of several genes that may play a role in FSHD. This type of genetic problem has never before been identified in a human disease.

FSHD is the third most common inherited neuromuscular disorder, affecting 1 in every 20,000 people. Symptoms include progressive muscle degeneration that primarily affects the face, shoulder blades, and upper arms. Despite intensive efforts, researchers have been unable to identify any genes that are altered in this disorder. Scientists can now focus on identifying which genes on chromosome 4 contribute to FSHD and how to regulate gene activity.

Deafness Gene Discovered	Return to Top

NIH researchers, in collaboration with 21 other scientists in this country, Pakistan, and India, have discovered a gene that, when mutated, causes two forms of deafness in both humans and mice.

The gene, called TMC1 for transmembrane cochlear-expressed gene, is located on chromosome 9 in humans and codes for a protein that is thought to affect the function of cochlear hair cells. Hair cells convert sound vibrations into electrical signals that are transmitted to the brain. One type of dominant hearing loss, called DFNA36, develops when one parent passes along a dominant mutation of TMC1. Although the child will have normal hearing early on, severe deafness will generally occur by the age of 30. A recessive form of deafness, called DFNB/B11, appears to be caused by a different mutation of TMC1. A child who inherits two copies of the recessive mutation will be deaf at birth. However, carriers with only one recessive mutation of TMC1 have normal hearing.

The researchers also reported that in mice, a similar gene, Tmc1, is located on chromosome 19. Mice with a recessive form of the mutant gene are profoundly deaf, and their cochlear hair cells do not respond to sound. The findings suggest that the protein encoded for by TMC1 in humans and Tmc1 in mice plays an important role in the function of cochlear hair cells. By identifying the role of this protein, researchers can better understand the hearing process and why some inherited hearing disorders arise.

Biodefense and Anthrax	Return to Top

The terror and fear felt by all Americans following September 11, 2001, has been devastating. The incidents of anthrax poisoning that followed raised the specter that the threat of bioterrorism is more real than perhaps anyone ever realized. The attacks have underscored the importance of understanding the mode of action of anthrax and other agents of bioterrorism.

Two teams of NIH-funded researchers recently reported key discoveries that shed light on how the anthrax toxin destroys cells, often killing its victims. In the most dangerous form of anthrax poisoning, inhalation anthrax, bacterial spores are inhaled and travel to the lungs, where they multiply and produce a lethal toxin. The anthrax toxin has three parts. Protective antigen (PA) binds to a receptor on the surface of cells and ushers edema factor and lethal factor into the cells of the host. Once inside the cell, edema factor and lethal factor interfere with cell metabolism, ultimately leading to cellular destruction. In the recent studies, researchers discovered that the first step in the attack of the anthrax toxin occurs when PA binds to a protein on the surface of animal cells that appears to be the anthrax toxin receptor. The researchers identified the specific portion of the receptor protein that binds to the toxin. Then they manufactured a truncated, synthetic version of that part of the receptor—the toxin-binding domain—that binds to the anthrax toxin. When they mixed the receptor fragment with the anthrax toxin, the fragment blocked binding of anthrax to its receptor. This approach suggests a plausible route to developing antidotes to the anthrax toxin.

Benefits of Biomedical Research	Return to Top

NIH invests its research dollars with the ultimate goal of preventing and treating disease and disability. This investment has benefited Americans by saving lives, improving the quality of life, and reducing the costs of health care and lost income due to disability.

Research Saves Lives. Over the past several decades, biomedical research has led to countless improvements in the health of the Nation:

• Heart Disease—Although heart disease is still the number one killer in the United States, the heart disease death rate (number of deaths per 100,000 people) dropped by 36 percent between 1977 and 1999.
• Stroke—The death rate due to stroke decreased by 50 percent between 1977 and 1999. And anticlotting medications have cut the risk of stroke due to atrial fibrillation, a common heart condition, by 80 percent.
• Cancer—Advances in understanding the genetic and environmental causes of cancer have led to effective screening programs that prevent cancer, improve detection, and increase the success of treatments. Between 1992 and 1998, the overall incidence of cancer fell 1.1 percent each year. The number of deaths due to cancer also fell 1.1 percent per year during the same period.
• Mental Illness—New treatments for schizophrenia can reduce or eliminate the symptoms of schizophrenia—including hallucinations and delusions—in 80 percent of patients.
• Spinal Cord Injury—High doses of steroid given within the first 8 hours after injury can prevent paralysis and increase the likelihood of recovery in patients who have lost sensation or mobility.
• Diabetes—Maintaining tight control of blood glucose levels, blood pressure, and LDL (bad) cholesterol in people with diabetes with the help of new medications can lower the risk of debilitating complications of diabetes, including heart disease, stroke, nerve disease, eye disease, and kidney disease by more than 50 percent.
• Respiratory Distress Syndrome—Infant mortality due to respiratory distress syndrome, a condition caused by immaturity of the lungs, has decreased significantly due to the development of a new treatment (lung surfactant) that prevents lung collapse in premature infants.
• Infectious Diseases—Vaccines now prevent diseases that once killed and disabled millions of children and adults.
• Life Expectancy—In general, an infant born today can expect to live three decades longer than one born at the turn of the last century.

Research Saves Money. Not only does biomedical research save lives, it also reduces the costs of health care and the impact of lost earnings. For example, estrogen therapy can reduce the incidence of osteoporosis and hip fractures in postmenopausal women for an estimated annual savings of $333 million in patient-care costs.

Men with testicular cancer can now expect a 91 percent cure rate and an increased life expectancy of 40 years. Thus, a 17-year, $56 million investment in research on testicular cancer has led to an annual savings of $166 million.

The NIH BUDGET	Return to Top

NIH’s important role in the Nation’s biomedical research enterprise is reflected in the proposed fiscal year 2004 budget of $27.8 billion. In 2003, Congress appropriated $27.2 billion to NIH, which supported nearly 46,700 research project grants in universities, medical schools, and independent research institutions across the country.

Several biomedical research priority areas were identified in the President’s proposed NIH fiscal year 2003 budget. They included:

Investigator-Initiated Research—$15.2 billion for new, competing, and continuing grants to fund research projects initiated by individual investigators.

Cancer Research—$5.5 billion for cancer-related research. Of particular interest is the use of proteomics and sophisticated computer technology to detect and diagnose cancers and new drugs that specifically target proteins known to arise from genetic mutations that lead to cancer.

Biodefense Research—An increase by $1.47 billion to $1.75 billion for biodefense research. Most of this money was targeted to expand the effort to develop countermeasures that will be needed to respond to bioterrorism attacks.

Clinical Research—NIH hopes to benefit from unprecedented advances in genomics, proteomics, and advanced imaging technology to test new ways to prevent, diagnose, and treat many diseases through clinical trials involving patients and healthy volunteers. The fiscal year 2003 budget placed particular emphasis on clinical research. For example, funds for the Extramural Loan Repayment Program for Clinical Researchers doubled to approximately $50 million over the previous year’s request.

Research on Disease Prevention—More than $6.8 billion to launch new initiatives to develop strategies to prevent disease. The cornerstone of disease prevention remains vaccine development. New vaccines to prevent otitis media, Ebola, HIV/AIDS, Leishmania, and malaria will be pursued.

Diabetes—More than $845 million to support research into the treatment and prevention of diabetes, a chronic disease that affects more than 17 million people in the United States today. Research into preventing type 2 diabetes through changing lifestyle factors as well as developing technology for islet cell transplantation to treat patients with type 1 diabetes will be emphasized.

Minority Health and Health Disparities—NIH remains committed to eliminating disparities in health among minorities and other disadvantaged populations. The proposed budget will support improvements to infrastructure in minority institutions and foster partnerships with minority research institutions. In 2000, Congress authorized the establishment of the National Center on Minority Health and Health Disparities, which aims to promote minority health and to lead the NIH effort to reduce and ultimately eliminate health disparities.

Parkinson’s Disease—NIH will continue to fund research to treat Parkinson’s disease, based on advances in understanding the genetics, cell biology, and pharmacology of the disease. Methods for replacing damaged dopamine-releasing neurons, as well as testing neuroprotectant drugs, which slow progression of the disease, will be actively investigated. The $215 million budget for this disease seeks to carry out the NIH Parkinson’s Disease Research Agenda, the result of a 2000 workshop attended by patients, doctors, and scientists from academia, government, and industry.

Future Directions	Return to Top

Although NIH-supported scientists have made many important discoveries in recent years, much remains to be done. Researchers are trying to find better ways to prevent and treat a wide range of diseases, including brain disorders, diabetes, cardiovascular disease, asthma, childhood diseases, and those associated with aging. Efforts to understand how organisms function under normal and abnormal conditions will lead to biomedical research advances that result in improved health for all Americans, and for people worldwide

NIH Research Training Programs	Return to Top

Programs for Undergraduate Students

Undergraduate Scholarship Program (UGSP)–The NIH UGSP offers scholarships to undergraduate students from disadvantaged backgrounds who are committed to careers in biomedical, behavioral, and social science health-related research. Applicants must be academically gifted and have earned an overall 3.5 grade point average, or be within the top 5 percent of their class. The yearly renewable scholarships pay for tuition and related educational and reasonable living expenses up to $20,000 per academic year.

Two kinds of service obligations are required from each scholarship recipient: after each scholarship year, recipients train for 10 weeks during the summer at the NIH laboratories as paid Federal employees, and after graduation recipients serve as NIH employees 1 year (52 weeks) for each year of scholarship support. Although these are required service obligations to NIH, the obligations themselves can be considered benefits—providing students with valuable research experiences. Additionally, students receive stipends during their service at NIH. The amount of the stipend varies according to the research experience of each participant.

Unique features of the UGSP include its mentoring activities and communication-skills training, which are designed to nurture the undergraduates’ career development, and practical experience in a state-of-the-art research setting.

Summer Internship Program in Biomedical Research (SIP)–NIH’s SIP offers opportunities for high school, undergraduate, and graduate students to spend at least 8 weeks conducting research in one of NIH’s research laboratories during the summer months. Students are encouraged to participate in meetings in their individual laboratories and have the opportunity to present the results of their research at the Summer Research Program Poster Day. Stipends range from $1,100 for high school students to $2,400 per month for advanced graduate students. Candidates must be permanent residents or citizens of the United States.

Programs for Predoctoral Students	Return to Top

The NIH Academy–The NIH Academy is a year-long postbaccalaureate research training program for recent college graduates who have demonstrated a well-defined interest in health disparities. The mission of the Academy is to enhance health disparities research through the development of a diverse cadre of biomedical researchers.

In addition to biomedical research training, there are two educational components to the program: seminars and workshops on topics related to health disparities and general knowledge workshops.

Predoctoral Intramural Research Training Awards–The goal of these awards is to introduce recent college graduates to biomedical research, as well as to provide additional time to pursue successful application to a doctoral-degree program. Participants receive training and gain research experience under the mentorship of an experienced clinical or laboratory investigator. Candidates must be U.S. citizens or permanent residents and have graduated from an accredited college or university no more than 12 months prior to arriving at NIH. Applicants must intend to apply to graduate or medical school within the next year.

Interim or Year-Off Intramural Research Training Awards–These awards are for graduate students or medical students who desire an interim or year-off research experience at NIH. Awards may be granted to students who have been accepted into graduate or medical school and who wish to delay matriculation. Students currently enrolled and attending graduate school are also eligible. Awards initially made for less than 1 year may be extended, but the cumulative period will not exceed 1 year.

Clinical Research Training Program (CRTP)–The CRTP is an individualized, 1- to 2- year tutorial for third-year medical and dental students. The program emphasizes clinical research training and coursework. It offers training with a senior research clinician in the student’s field of research interest. CRTP scholars receive stipends of $25,300 per year, health insurance, and reimbursement for traveling and moving costs. Clinical research scholars must be U.S. citizens or permanent residents and gain their dean’s permission to take a leave of absence from their studies.

Programs for Physicians and Postdoctoral Researchers	Return to Top

Loan Repayment Programs (LRPs)–The NIH LRPs offer educational loan repayment assistance to recent medical school graduates and postdoctoral scientists. NIH offers both intramural LRPs for researchers employed at NIH and extramural LRPs for investigators conducting qualified research at nonprofit institutions, funded by nonprofit or U.S. Government (Federal, State, or local) entities.

The LRPs can repay up to $35,000 per year for each year of support (with a minimum 2- or 3-year contract), depending on total debt. The LRPs also provide reimbursement for any Federal and State tax liabilities that result from the loan repayments.

There are currently five extramural LRPs, each of which seeks to attract investigators to a particular area of research: clinical (two programs), pediatric, health disparities, and contraceptive and infertility research.

There are three intramural LRPs (for AIDS, clinical, and general research), which repay up to $35,000 in debt per year, depending on total debt, as well as a special initiative for the Accreditation Council for Graduate Medical Education (ACGME) Fellows, which offers $15,000 per year in loan repayment to fellows in subspecialty and residency training programs accredited by the ACGME.

A primary goal of the intramural LRPs is to attract the best and brightest postdoctoral and medical school graduates to NIH.

Laboratory Research Pathway–Participants who enter this postdoctoral training pathway engage in pure laboratory research. Applicants must have either a graduate doctoral degree (e.g., Ph.D. or M.D/Ph.D.) or a professional degree (e.g., M.D., D.O., D.D.S., D.M.D., or D.V.M.) accompanied by previous research laboratory experience.

Combined Clinical and Research Pathway–In this postdoctoral training pathway, participants often receive clinical subspecialty training as well as training in basic research. Applicants must possess a degree in medicine or dentistry. In general, candidates must have 2 or 3 years of postgraduate clinical training and ideally should apply 1 or 2 years before the desired date of the appointment. In the first year of training, the Clinical Associate is involved in clinical research and care on the wards of the NIH Clinical Center. In the second and optional third years, the Clinical Associate may choose a training program that will involve clinical research, basic research, or a combination of the two. The Clinical Associate experience in many cases is creditable toward board certification.

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NIH maintains a comprehensive site on the World Wide Web at http://www.nih.gov. The site contains information about the agency’s scientific research programs, the Institutes and Centers that conduct intramural research and administer extramural grants, news about recent research findings, health resources for the public, and information about research training programs.

For more information about training opportunities at NIH, visit the following individual Web sites:

NIH Undergraduate Scholarship Program: http://www.ugsp.nih.gov

NIH Loan Repayment Program: http://www.lrp.nih.gov

List of training programs at NIH and general information from the NIH Office of Education:
http://www.training.nih.gov

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