The Ad Hoc Group for
Medical Research Funding

Other sections of the Ad Hoc Group's proposal:

Executive Summary

Why Double?

What Investments are Needed?

How Does NIH Decide Priorities and Ensure Accountability?

How Do We Ensure That Progress Continues?

Research performed by NIH-supported investigators results in countless medical advances that have directly benefited the lives of all Americans. By investing in medical research at NIH, the Federal Government ensures America is positioned to meet present and future health needs.

An important benefit the effort to double NIH has brought us so far is that we are funding more grants, and therefore pursuing a greater percentage of scientific opportunities than in previous years. The total number of research project grants that NIH can support has risen by nearly seven thousand -- from over 28,000 in 1998 to between 34,000 and 35,000 in 2001, the third year of doubling. During this period, the percentage of ideas submitted to NIH that can be funded has risen. These numbers represent thousands of research ideas that would not have been pursued without the effort to double NIH - efforts that, if history is any guide, contain some mix of modest research advances and revolutionary leaps forward that, in aggregate, have led to the greatest improvements in health in history. Yet, in spite of these increases, NIH still leaves many good ideas unexplored each year, and the competition for grant funding remains keen.

Doubling the NIH budget has been an important investment in our future already, and continuing the effort will ensure that we are able to bring the total number of grants funded closer to 40,000 and the chances of a well-thought out research proposal being funded up to one-third - which promise to produce thousands more research advances that would not otherwise be pursued, to the detriment of our nation's health.

Much of the work NIH presently supports is built on years of advances from NIH investigator-initiated research. Since scientific research is not linear, new discoveries depend on past, current, and future investments in medical research. Sustaining the research continuum requires an investment in new technologies and methodologies as well as advancing the scientific progress from past investments in NIH. For example, investments in NIH-funded research have:

Developed a vaccine to nearly eradicate Hib - As recently as 10 years ago, the bacterium known as Haemophilus influenzae type b (Hib) caused 16,000 to 25,000 children in the United States per year to develop disease. One of the most serious complications of Hib disease was meningitis, which occurred in 60 percent of affected children. Of those children stricken by meningitis, 10 percent died and many more suffered permanent health consequences such as hearing loss and mental retardation.

Thanks to NIH-sponsored research, vaccines have been developed that decreased Hib disease by 95 percent worldwide. From the introduction of an Hib vaccine in the mid-1980's and an improved version that boosted the immunity of infants, researchers were able to ensure the protection of children as young as two months old. The cost savings from the dramatic reduction in the incidence of Hib is conservatively estimated at more than $400 million per year for the treatment and long-term care of children with meningitis and other Hib-related diseases. Many of the principles that researchers used to make the Hib vaccine safe for even small children are now being applied to other diseases and hold the promise of even greater public health applications.

Advanced our understanding of diabetes - An estimated 16 millions Americans have diabetes. Type 1 diabetes - an autoimmune disease where the body's own immune system destroys the insulin producing cells in the pancreas - develops most often in children or young adults, although the disorder can appear at any age. Transplantation of the pancreas or the insulin producing cells offer the best hope of cure for type 1 diabetes; however, people with transplants must take powerful and costly drugs to prevent rejection of the transplanted organ, which may eventually lead to other health problems. Recently, researchers at the University of Alberta, announced promising results with pancreatic islet transplantation in seven patients with type 1 diabetes. At the time of the report in the New England Journal of Medicine, all seven patients remained free of the need for insulin injections up to 14 months after the procedure. A clinical trial funded by the NIH and the Juvenile Diabetes Research Foundation will try to replicate the Edmonton advance. With the insights gained from this trial and other research, scientists hope to further refine methods to harvest and transplant the insulin producing cells and learn more about the immune processes that affect rejection and acceptance of the transplanted cells.

The more common form of diabetes is type 2, which is most common in adults over age 55. In type 2 diabetes, the pancreas usually produces enough insulin, but for unknown reasons, the body cannot use this insulin effectively. After several years, insulin production decreases. NIH-supported research has resulted in the groundbreaking discovery of Calpain-10 as a type 2 diabetes susceptibility gene. This breakthrough marks the first successful identification of a specific gene implicated in a "complex genetic disease" and underscores the value of long-term investment in the tools of modern molecular genetics. The discovery of Calpain-10 offers new promise for patients with type 2 diabetes, which disproportionately affects minority groups and causes many debilitating complications such as eye, kidney, nerve, and heart damage.

Utilized structural MRI measurements to predict who will get Alzheimer's disease - Researchers are using structural magnetic resonance imaging (MRI) measurements to determine whether cognitively normal older persons and persons in the very early phase of Alzheimer's disease could be identified before they developed clinically diagnosed Alzheimer's. An NIH-funded study discovered that an MRI scan could identify people who would develop Alzheimer's disease over time based on measurements of four brain regions.

The MRIs were 100% accurate in discriminating between the participants who were normal and those who already had mild Alzheimer's as well as 93% accurate in discerning participants who were normal and those who initially had memory impairments and ultimately developed Alzheimer's disease. This study offers evidence establishing the involvement of specific areas of the brain in the early pathology of Alzheimer's and suggests that it may be possible to better identify people at greatest risk and those for whom early treatment could make a difference. Although the MRI technique needs to be further refined and validated before it can be used in everyday medical practice, this study is a promising advance in predicting who will get Alzheimer's disease.

Advanced the treatment of depression and schizophrenia - An estimated 19 million Americans suffer from depression and 2 million from schizophrenia. Thanks in part to NIH-sponsored research, the diagnostic and treatment tools available for mental illness provide many Americans struggling with mental illness the opportunity to lead normal lives. The Nobel Prize in physiology or medicine for 2000 was awarded to two long-time National Institute of Mental Health grantees. Their research on signal transduction in the nervous system improved treatments for Parkinson's Disease, schizophrenia and depression. A 2000 Medal of Science was awarded to another NIMH grantee for advances in modeling neural circuit disruption.

Uncovered a hormone involved in the onset of osteoporosis - For patients with osteoporosis - most of whom are postmenopausal women - parathyroid hormone (PTH) now offers the unprecedented possibility of building new bone to replace bone made thin and breakable by this widespread disease. This advance is one of the fruits of long-term research, which has amassed incremental knowledge about the endocrine and metabolic processes of bone formation and reabsorption; the roles of exercise, calcium, vitamins, and hormones (such as estrogen and PTH) in maintaining bone integrity; and the refinement of methods to measure bone density and thus better diagnose and monitor the disease.

Impressive NIH-funded studies have led to the identification and cloning of a calcium-sensing receptor, which has defined an important step in the pathway that regulates whether PTH will signal cells to either increase or to decrease production of bone minerals. Because of the enormous therapeutic potential these findings represent, a goal of further research is to produce PTH in a form suitable for oral administration. Then, it might be combined with existing oral agents in a treatment approach that both promotes bone formation and inhibits bone loss for the maximum benefit of patients. The prospect of such a new combined therapy would be of enormous benefit to the 10 million Americans who currently have osteoporosis, as well as to the estimated 18 million others whose low bone density places them at serious risk for the disease.

Grown replacement heart valves in the laboratory - A group of NIH-supported researchers used a tissue-engineering technique to "grow" heart valves in their laboratory and implanted them into six lambs. Heart valves are flap-like structures that help regulate blood flow through the heart and, when malfunctioning, can seriously impede heart function. Although there are major problems associated with each type of valve replacement, more than 60,000 patients in the United States undergo replacement surgery annually.

All the heart valves grown by this group of researchers functioned satisfactorily for up to five months. More important, the valves gradually evolved to resemble natural valves in terms of several mechanical and structural characteristics. Further development of tissue-engineering systems like the one developed in this study could result in heart valves that are far better than the ones in use today. Tissue-engineered heart valves might be able to function for the remainder of a patient's life, provide ongoing tissue alteration and repair as needed, and, in the case of pediatric patients, grow with the patient.