When support for basic research is adjusted to 

 take account of inflation, the adjusted dollars indi- 

 cate that basic research support advanced from a 

 level of approximately $275 million in 1965 to 

 around $297.5 million 10 years later, a far less 

 dramatic increase than the current dollar figures 

 suggest. 



Most of NIH's basic research is performed in 

 extramural institutions, particularly in universities 

 and colleges (including the Nation's medical 

 schools). While the intramural portion of dollar 

 support has increased comparatively slowly over 

 the years, the dollar amount going to extramural 

 institutions for support of basic research has 

 climbed from about $35 million in 1958 to a 1975 

 figure of close to $424 million (Figure 2). The pro- 

 portion of extramural funding as a percent of the 

 total has also increased during this time, from 74 

 percent to 82 percent. Universities and colleges 

 have continued as the predominant performers of 

 basic research. Others include independent re- 

 search institutes and operating foundations, feder- 

 ally funded R&D centers, industrial firms. State 

 and local governments, and private individuals. 



Basic research will continue to play a critical 

 role in the total R&D eflFort at NIH by providing 

 the fundamental knowledge base upon which ap- 

 plied research and developmental eflforts must 

 build. And NIH will continue to rely on the Na- 

 tion's academic institutions to play a major part- 

 nership role in this continuing effort to improve 

 our understanding of life processes. 



Examples of Basic Research 



Besides dollars for research support, there is 

 another and more important measure of the role 

 and impact of basic research at NIH. It is found 

 in the scientific advances that have contributed 

 greatly to human health and well-being. A number 

 of examples of basic biomedical research achieve- 

 ments follow. It must be emphasized that this is 

 not a definitive listing of all such contributions. 

 Many other examples could be added, as noted in 

 NIH Research Advances, one of NIH's annual 

 publications (first published in 1975), or in Appen- 

 dix A of the Report of the President's Biomedical 

 Research Panel. 



Elucidation of Cellular and Molecular 

 Immunologic Actions 



The past 10 years have seen major advances in 

 scientific understanding of the immune system. 

 This is particularly true in regard to the activity of 

 certain cells and chemical molecules. 



It has been known for some time that, in the 

 immune response, two types of lymphocytes 

 (white blood cells) play major roles. These are the 

 T cells, which depend upon the thymus for their 

 maturation, and the B cells, which are derived 

 from the bone marrow. When a foreign antigen — 

 such as a bacterium, a virus, or an allergen — is in- 

 troduced into the body, both T and B cells partici- 

 pate in the formation of antibodies. Some types of 

 these blood proteins, generally protective when 

 formed against bacteria, are harmful in certain 

 naturally susceptible individuals when produced in 

 response to an allergenic substance. 



Drs. K. and T. Ishizaka, now at Johns Hopkins 

 University, were the first to identify a unique class 

 of antibodies — immunoglobulin E, or IgE — as 

 being specifically responsible for immediate hyper- 

 sensitivity reactions, or allergies. These grantees 

 of the National Institute of Allergy and Infectious 

 Diseases (NIAID) and others have shown that 

 when IgE fixes to certain cells, contact with aller- 

 gens such as pollens results in the release of chem- 

 ical molecules directly responsible for many of the 

 symptoms of allergies — wheezing, runny nose and 

 eyes, etc. Discovery of IgE thus constituted a criti- 

 cal turning point in the field of allergy research. 

 Information arising out of the delineation of IgE 

 function has made it possible to distinguish be- 

 tween those persons with asthma, rhinitis, dermati- 

 tis, etc., whose disease is of allergic origin and 

 those whose symptoms are similar but are due to 

 other mechanisms. As a result, proper treatment 

 programs can be instituted. 



T cells are also known to play a crucial role in 

 so-called cell-mediated immune responses, such as 

 those involved in graft rejection and in defense 

 against fungal infections. In these immune reac- 

 tions, a variety of chemical mediators, known as 

 lymphokines, may be released by contact of a spe- 

 cific antigen with previously sensitized T cells. 

 One of the first of these chemicals to be identified 

 is known as macrophage inhibition factor (MIF). 

 This soluble material inhibits the normal move- 

 ment of macrophages (scavenger cells) to the site 

 of tissue injury. Other factors have since been 

 found to affect the movement of white blood cells 

 such as neutrophils and eosinophils involved in 

 inflammation. Sensitized lymphocytes also pro- 

 duce interferon, important in defense against viral 

 infections, and transfer factor, intimately con- 

 cerned with cellular immunity. Both of these me- 

 diators have been extensively studied for possible 

 clinical usefulness. 



More recently it has been discovered that there 

 is a subpopulation of T cells that actually suppress- 

 es the cell-mediated immune response. For exam- 

 ple, NIAID grantees at the Mayo Medical School, 

 Rochester, Minn., have shown that patients with 



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