cial environment. This Panel commends neuro- 

 biology as a compelling long-range interest wor- 

 thy of national attention. 



From the many possible examples of highlights 

 of progress in the past 10 years, a few may be 

 cited: 



New and important details of nerve cell struc- 

 ture and interconnections have been revealed by 

 the use of freeze-fracture and scanning electron- 

 microscopic techniques. Calcium ions have been 

 shown to be essential for the release of transmit- 

 ter agents at nerve-to-nerve or nerve-to-muscle 

 connections. The neurotransmitter, dopamine, has 

 been recognized as a major factor controlling re- 

 lease from the pituitary of prolactin and growth 

 hormone. 



In stroke, the blood vessels of the brain have 

 been shown to be especially sensitive to hyperten- 

 sion, but unlike heart vessels, they are not sensi- 

 tive to elevated levels of cholesterol in the blood. 

 Moreover, the effects of high blood pressure and 

 the development of atherosclerosis in the brain 

 have been shown to be different from those in the 

 heart and general circulation. For epilepsy, the 

 reliable quantification of blood levels of anti-epi- 

 leptic drugs by clinical laboratories has been 

 achieved. 



In virally induced disease of the nervous sys- 

 tem in animals, the nature and effects of defective 

 interfering (DI) viral particles have been elucidat- 

 ed, so that we now know that DI particles prevent 

 normal replication and shedding of viruses from 

 host cells and thus either prevent spread of acute 

 infection or produce a chronic degenerative disor- 

 der. The study of viral infections and immune 

 responses of host animals has been facilitated by 

 the introduction of a new sensitive, inexpensive 

 procedure called enzyme-linked immunosorbant 

 assay (ELISA). Viral probes and DNA hybridiza- 

 tion techniques have also become important tools 

 for studying the mechanisms of viral and immu- 

 nological diseases and the role of T-lymphocytes 

 in cell-mediated immune responses in the nervous 

 system. These studies of cell-mediated immunity 

 have relevance for multiple sclerosis and amy- 

 otrophic lateral sclerosis (ALS). 



A great deal of progress has been made possible 

 because of the development of other highly spe- 

 cialized new instruments and techniques. One 

 example is the newer generation of computerized 

 axial tomographic (CAT) brain and body scan- 

 ners. At the resolution now available, CAT scans 

 of the brain reveal details of anatomical structures 

 and pathological changes (especially demyelina- 

 tion) hitherto available only from invasive tech- 

 niques. Moreover, the computerized scans can be 

 converted from the original axial or cross-sec- 

 tional scans of the spinal cord into views in the 



longitudinal plane, so that the extent of abnormal- 

 ities and their relationship to other structures are 

 clear. Computerized axial tomography will contin- 

 ue to have an extraordinary impact on diagnostic 

 radiology and clinical management, especially in 

 the neurological and communicative disorders. 



Another advance has resulted from the discov- 

 ery that there is a shortage of dopamine in the 

 brains of patients with Parkinson's disease. This 

 important finding clearly pointed to the possibility 

 of replacement therapy, and led to efforts to treat 

 Parkinson's disease with L-dopa. Improvements 

 in drug therapy have since been made, and pro- 

 gress in the drug treatment of Parkinsonism ranks 

 as one of the major neurological success stories 

 of the past decade. 



Receptors for Hormones, Transmitters, and 

 Drugs 



Of broad significance have been the identifica- 

 tion and isolation of receptors for hormones, 

 transmitters, and drugs and the recognition that 

 many hormones produce effects through a second- 

 ary messenger molecule. The findings help explain 

 the ability of the endocrine system to accomplish 

 both specificity and integration. 



Research on receptors has played a significant 

 role in improved clinical management of such 

 metabolic diseases as diabetes, through the devel- 

 opment of new knowledge about insulin. 



Insulin is manufactured in the pancreas, re- 

 leased into the bloodstream, and distributed to 

 cells throughout the body. For insulin to activate 

 a cell, the hormone first binds to specific recep- 

 tors located on the cell surface. There, receptors 

 serve two major functions: (1) They act to distin- 

 guish insulin from other molecules to which they 

 are exposed, and then bind the insulin tightly at 

 the cell surface; (2) the combination of hormone 

 with receptor initiates a signal that activates in- 

 tracellular processes characteristic of insulin ac- 

 tion. 



Dr. Jesse Roth and his associates at the Nation- 

 al Institute of Arthritis, Metabolism, and Diges- 

 tive Diseases (NIAMDD) devised methods to 

 measure precisely the binding of insulin to specif- 

 ic receptors on cells. They found that both the 

 number of receptors per unit of cell surface and 

 the tightness with which each receptor binds insu- 

 lin may undergo changes. These alterations, 

 which were largely unsuspected, influence the 

 effectiveness of a given amount of insulin. In 

 obese persons, and experimentally in obese mice, 

 the number of insulin receptors per cell was found 

 to be subnormal, which accounts for much of the 

 decreased responsiveness to this hormone. 

 Moreover, when obesity is controlled and weight 

 becomes normal, blood glucose and insulin levels 



HEALTH. EDUCATION AND WELFARE 105 



