ROLE OF STEROLS IN HEALTH AND DISEASE

(L. F. Fieser, Harvard University, investigator)

Under partial support from NSF, Dr. Fieser has identified and isolated a chemical compound showing antibiotic properties which may find significant use both in therapy and industry.

Dr. Fieser has been studying a group of chemical compounds known as quinones which are distributed widely among plants and animals. Among others, he singled out for investigation a pigment known as gonyleptidine which is secreted by a spider found in Uruguay. Through the application of quinone chemistry, the components of this pigment were isolated. Although known, these substances had been neglected previously. However, they were found to have considerably greater antibiotic activity than all of many other quinones investigated.

Having determined the structure of the compound, it was possible to produce it synthetically-at a cost which proved to be low. It is now under study by biological and medical groups and the pharmaceutical industry for use in therapy and for certain industrial uses (e.g., as sporicides in the paper industry).

METASTABLE BOILING

(Dr. J. W. Westwater, University of Illinois, investigator)

Working with the help of an NSF grant, Dr. Westwater developed a new method for studying the boiling of liquids, which may aid in the development of fundamental equations for predicting heat transfer rates in the different regions of boiling.

It is a curious fact that some of the most familiar phenomena in nature are among the least understood. So it is with the boiling process. It has been known for some time (since 1934) that three distinct types of boiling existed— nucleate, transition, and film boiling. To the eye, they are distinctly different. An experienced worker can even distinguish them by ear. In a typical test, the noise rises from 2 to 18 and then to 26 decibels as the boiling progresses from nuclear to transition to film boiling. The heat transfer properties are, also, decidedly different, being more efficient in some stages than in others. Still much was to be learned about the nature of boiling, its physical properties, and how to control it.

The mystery has recently been further pursued by Dr. Westwater under an NSF-supported project entitled "Metastable Boiling." As a result, Dr. Westwater has clarified the difference between the three types of boiling. A set of still photographs was obtained at a film exposure time of one-millionth of a second, and motion pictures were taken at a rate of 4,000 frames per second of alcohol (methanol) boiling at atmospheric pressure. The most important discovery from Dr. Westwater's experiments was that boiling is a very orderly process when slowed down by the slow motion camera and not the apparently confused phenomenon viewed by the naked eye (figs. 6a and 6b). The various stages of this observed process are summarized below.

In nuclear boiling-the usual boiling that occurs in a teakettle-bubbles form on the hot surface with great speed. As soon as one bubble breaks loose, a new one forms at precisely the same point on the hot surface and the surface seems to be peppered with active points. Heat transfer is most effective in this state and depends primarily on the number of active points which in turn is dependent upon the temperature of the hot generating surface. of methanol, 17 bubbles per second and of 0.17 inch diameter were formed at each active point. At a certain critical temperature, however, a dramatic change takes place in the boiling process. The heat transfer rate decreases considerably, the boiling becomes noticeably louder, and the pictures show a series of small explosions occurring along the solid surface of the fluid. For methanol, the burst occurred 84 times per second and the generation of bubbles is random. A vapor film forms over the surface of the fluid at this stage and when the vapor film becomes thick it smothers the vapor burst resulting in the final type of boiling-film boiling. Heat transfer and vapor generation fall to their lowest value even though the temperature is relatively high. No explosive bursts can be seen at this stage, but loud drumlike noises rumble from the liquid. New vapor is formed at the surface of the vapor-fluid interface and not on the solid surface of the heating element. Ripples of vapor emerge in a gentle wave motion at 74 waves per second for the methanol at this stage.

FIGURE 6b. Boiling in the film manner. Methyl alcohol is boiling outside a copper tube (dark portion of picture) which is far hotter than the boiling liquid. Bubbles are released at the top of the tube only.

Dr. Westwater's research has resulted in a significant addition to existing knowledge of a basic physical process. It has attracted a great deal of interest among scientists and has already resulted in numerous publications in a particularly wide variety of technical journals.

RELATION OF LIVER DISEASE TO CERTAIN MENTAL DISORDERS

Dr. S. P. Bessman, University of Maryland School of Medicine, Investigator Basic research conducted by Dr. Bessman under an NSF grant has produced findings as to the relationship between liver disease and mental symptoms which may have widespread clinical value.

All the changes which take place between the moment of entry of a foodstuff into an organism and the moment of discharge of its products into the environment are included in the field of intermediary metabolism. As understanding of this area has increased recently, attention has become focused upon certain small molecules or organic fragments which appear repeatedly in the various pathways of the metabolic process.

Dr. Bessman has been investigating the fate of certain of these fragments (acetyl groups) in the liver, their utilization in the synthesis of specific compounds, and the subsequent production of energy which results. During the investigation of these reactions, his interest was directed to the role of ammonia which normally is produced in the intestinal tract and is removed from the blood by the liver.

It has long been known that patients with liver disease frequently exhibit mental symptoms, and that in many cases, these symptoms become severe enough to cause convulsions. coma, and eventual death and it has been suggested that this complex of symptoms results from the toxic effects of the accumulation of ammonia in the blood. Dr. Bessman has been able to demonstrate that this excess ammonia is taken up by the cells of the brain where it appears to reverse a specific chemical reaction normally occurring there. This, in turn, leads to the inability of the brain to utilize oxygen properly.

This investigation may have clinical value in the treatment of many diseases other than liver disease, since it has been shown that the mental symptoms associated with heart disease, intestinal obstruction, and possible sepsis are either caused by or seriously augmented by increased ammonia concentration in the blood. At present, Dr. Bessman is attempting to find specific methods of enhancing the normal utilization of ammonia.

SYNTHESIS OF DL-TESTESTERONE

Dr. William S. Johnson, University of Wisconsin, Investigator

The organic chemical research conducted by Dr. Johnson, with NSF support, has been directed toward the synthesis of structures related to the steroids. A notable advance during the past year has been the successful, complete total synthesis of the hitherto unknown DL-testesterone. Resolution of this racemate yields d-testesterone, which is identical to the natural male hormone. Significant progress has also been made toward the total synthesis of 11-oxygenated steroids (of which cortisone is an example) in which the oxygen at C1 is introduced at an early stage of the synthesis.

BETTER UNDERSTANDING OF THE FUNDAMENTAL DISORDER OF DIABETES

Dr. Rachmiel Levine, Michael Reese Hospital, Chicago, Investigator All living organisms are composed of cells and, in order to function and survive, these individual cells must receive nourishment and excrete waste products. Such substances (nutrients, waste product, etc.) must pass through the membrane which surrounds each cell. Thus, this membrane must be permeable but yet selectively so-otherwise there would be uncontrolled migration of necessary and/or deleterious substances out of or into the cell.

This fundamental vital process is not at all clearly understood and is at present a very active field of investigation. NSF is supporting a number of studies in this field, all of which are showing good progress, but a most interesting and important finding has resulted from the work done with the aid of NSF support by Dr. Rachmiel Levine of Michael Reese Hospital. In his work on transport of substances through the cellular membrane, Dr. Levine directed particular