some adaptive advantage. 



Occasionally these virus-like genes can be "ac- 

 tivated" by chemicals to begin forming complete 

 viral particles, but the cells they inhabit usually 

 do not acquire aberrant growth characteristics as 

 a result. 



Conversely, actual cancer-like change in the 

 growth patterns of cells caused by RNA tumor 

 viruses is highly selective: Of the various types of 

 cells they infect, specific viruses "transform" 

 only certain kinds. The fact that reproduction and 

 transformation functions can be separated sug- 

 gests that they are under the control of different 

 viral genes, and molecular biologists are now 

 working to identify the protein products of var- 

 ious genes to understand better their mechanism 

 of action. This information is vital for an under- 

 standing of carcinogenesis, but in addition, it may 

 be useful in clarifying certain questions in devel- 

 opmental biology, because of the specificity be- 

 tween tumor viruses and the cells they are able to 

 transform. 



The discovery of reverse transcriptase has been 

 applied in many other ways to research in basic 

 and applied biology: 



1. Reverse transcriptase assays have become a 

 sensitive and relatively inexpensive method for 

 measuring the quantity of RNA tumor virus pre- 

 sent in cell cultures, animal tissues, or sera known 

 to contain virus. 



2. In perhaps the major application of reverse 

 transcriptase to biology, numerous scientists have 

 used the enzyme with RNA of different RNA 

 tumor viruses as a template to make DNA from 

 radio-labelled precursors. The DNA is then used 

 as a molecular probe for investigating the presence 

 of viral-related RNA or DNA molecules in animal 

 and human cells. 



3. Purified reverse transcriptase will use many 

 types of single-stranded RNA, in addition to viral 

 RNA, as template. Molecular biologists are using 

 radioactive DNA's synthesized from specific cel- 

 lular RNA templates to look in various types of 

 cells for RNA similar to the template, and to look 

 for the genes that coded for the RNA. 



4. The biochemical and immunological charac- 

 teristics of reverse transcriptase have been de- 

 fined so carefully that it can be distinguished read- 

 ily from the DNA-synthesizing enzymes (DNA 

 polymerases) of uninfected cells. Thus, detection 

 of reverse transcriptase has been used as an indi- 

 cator of the presence of RNA tumor viruses not 

 visible as whole particles. For example, the dis- 

 covery of this enzyme in blood cells of some per- 

 sons with leukemia was the first biochemical evi- 

 dence that RNA tumor viruses sometimes may be 

 present in humans. 



Organization and IVIanagement of 

 Scientific Activities 



These research contributions result from intra- 

 mural and extramural systems built upon a parti- 

 cular concern for encouraging and maintaining the 

 highest possible quality in research. 



The intramural system of NIH is under the 

 direction of the Deputy Director for Science (as- 

 sisted by the Assistant Director for Intramural 

 Affairs). Within each of the 10 Institutes that con- 

 duct intramural research (the National Institute of 

 General Medical Sciences does not have intramur- 

 al laboratories), a Scientific Director is responsi- 

 ble for the programs of the Institute. Collectively, 

 the Scientific Directors form a board chaired by 

 the Deputy Director for Science, with the Assist- 

 ant Director for Intramural Affairs serving as 

 Executive Secretary, this Board constitutes the 

 policymaking and staff promotion review forum 

 for intramural research at NIH. 



Within this system intramural research projects 

 are conceived, planned, and implemented by sci- 

 entists employed at NIH. It is evident that with 

 limited resources available to the in-house re- 

 search program, only certain research areas can 

 be pursued. These particular areas are defined by 

 the interests and expertise of the senior scientific 

 staff of each Institute. In guiding this staff, the 

 Scientific Director of the Institute (who is respon- 

 sible for administration and management of the 

 intramural programs) is advised by a Board of 

 Scientific Counselors — an outside group of con- 

 sultants who meet biannually to review intramural 

 scientists and their research projects and to ad- 

 vise the Scientific Director on allocation of re- 

 search resources. 



Intramural research proposals are normally 

 conceived and proposed by individual research 

 scientists and discussed extensively with Section 

 Heads, Laboratory or Branch Chiefs, and the 

 Scientific Director. Any of these proposals might 

 involve collaborative efforts with other scientists 

 in the same or another Institute at NIH, or with 

 scientists outside NIH. If it appears during this 

 review process that the basic ideas have consider- 

 able merit and that appropriate resources can be 

 made available, the NIH intramural scientists will 

 be permitted to begin. On a periodic basis after 

 the project has been initiated, the efforts are re- 

 viewed for quality and progress both by scientific 

 peers and administrative superiors and ultimately 

 by the Board of Scientific Counselors. 



This research progress review is supplemented 

 by a systematic promotion review process for in- 

 tramural scientists. Annually, the Deputy Director 

 for Science conducts a promotion review at which 

 each Scientific Director analyzes his entire organi- 



1 08 HEALTH. EDUCATION AND WELFARE 



