Zymosan, a yeast product, increases recoveries in tumor-bearing mice Dr. William T. Bradner, Sloan-Kettering Institute for Cancer Research, has reported that injection of a single low dose of the yeast product, zymosan, into the body cavity of tumor-bearing Swiss mice significantly increased recovery of the mice. After about 2 weeks, 60 percent of the tumors in treated animals were destroyed and were completely extruded, as compared with 6 percent of tumors in controls. Injection of a very large dose had significantly less effect; only 28 percent of the animals lost their tumors. Zymosan tested against the same tumor grown in tissue culture had no direct effect on the cancer cells. It is concluded that a host-mediated phenomenon appears to be responsible for the loss of tumors by zymosan-treated animals. Continuous therapy is best for leukemic mice The formulation of correct dosage schedules remains one of the chief problems in cancer chemotherapy. A series of studies is being made by scientists of the Laboratory of Chemical Pharmacology and the Biometry Branch to develop optimum-treatment schedules in the management of mouse leukemia with methotrexate. One project was conducted to determine the influence of the duration of treatment of advanced mouse leukemia with methotrexate, since an earlier study had suggested that failure to achieve cures was due principally to the chronic toxic effects of the drug resulting from prolonged treatment. John M. Venditti, Laboratory of Chemical Pharmacology, has now reported that it is not advantageous to discontinue the daily injections in order to allow the host animal to recover from the toxic effects of the drug. In the study, treatment of the test mice was started on the 8th day following innoculation with leukemia. Control mice, which received no drug treatment, survived an average of 2.2 days longer, or 10.2 days. Treated mice survived at least 12 days longer, or a total of 20 days after inoculation. However, when daily treatment was discontinued, the mice survived only 2 to 3 days. These results suggest that the drug, as given under this dosage schedule, did not produce sufficiently extensive regression of advanced tumors to permit discontinuation of treatment in an effort to control toxicity. Combined dose schedule held superior in treating leukemia in children As a result of a study of the effects of 6-mercaptopurine in the treatment of acute leukemia in children, Dr. Carol B. Hyman, University of Southern California, suggests that an initially high dose rate followed by a smaller dose rate would produce the best therapeutic results. The literature indicates that 6.6 miligrams of the drug per kilogram of body weight approaches the maximum daily dose that can be taken by the majority of patients without serious toxic reactions. Dr. Hyman has now reported that this dose rate reduces the interval between the start of therapy and the onset of remission and that serious toxic reactions do not appear during the first 2 weeks of therapy on this schedule. A maintenance dose of 2.2 milligrams per kilogram per day of the drug produces longer remissions, Dr. Hyman reports. Hence, a combined dosage schedule would seem to be advantageous because of the shortened period preceding onset of remission and the benefits of continuous therapy. Drugs sensitize tumor; increase effectiveness of radiation therapy In studies of combination therapy, experiments on the treatment of cancer in mice show that sensitization of a tumor by anticancer drugs augments the effectiveness of radiation therapy. Dr. Morton Kligerman, College of Physicians and Surgeons, Columbia University, has reported that mammary tumors of mice treated by both chemical and radiation therapy exhibited more therapeutic response than did those treated by X-rays or chemicals alone. The effect of therapy was measured on the basis of percentage of tumors showing regression, degree of regression, "cure rate," and average weight of tumors at the end of a 1-month observation period. These findings suggest that the limit of curability of cancer by radiation therapy is no longer determined by a lack of sufficiently powerful radiation sources, and that tumor sensitization by biochemical means appears to be an important method of increasing the response of tumor cells as compared with that of normal tissue. Study therapeutic effect of multidrug treatment On the assumption that quantitative biochemical differences between tumor and host may serve as a basis for cancer chemotherapy, investigators of the College of Physicians and Surgeons, Columbia University, are studying the use of multidrug therapy to exploit such differences to a point at which maximum anticancer effect and minimum toxic effect against the host are achieved. Dr. Daniel M. Shapiro has reported on results of tests using 6-aminonicotinamide (6-AN), which exerts strong antitumor activity against mammary Adenocarcinoma 755 in mice. Tumor regression was accompanied by marked weight loss at high dose levels and less weight loss at low dose levels. Combination of the drug at low dose levels with 8-azaguanine resulted in tumor regression without appreciable weight loss in the host. Addition of testosterone (male sex hormone) to this double combination further reduced weight loss without changing the degree of tumor regression. The fact that 6-AN is a potent antagonist of niacin (one of the B-vitamins) emphasizes the potentialities of vitamin antagonists and suggests that niacin antagonists be investigated as a source of anticancer agents. MENTAL HEALTH ACTIVITIES WEDNESDAY, FEBRUARY 19, 1958. WITNESSES DR. ROBERT H. FELIX, DIRECTOR, NATIONAL INSTITUTE OF MENTAL HEALTH DR. JAMES A. SHANNON, DIRECTOR, NATIONAL INSTITUTES OF HEALTH DR. C. J. VAN SLYKE, ASSOCIATE DIRECTOR, NATIONAL INSTITUTES OF HEALTH Mr. FOGARTY. The committee will come to order. We have before us now the request for the Mental Health Institute. GENERAL STATEMENT Dr. Felix, do you have a statement for the committee? Dr. FELIX. I have submitted a formal prepared statement. (Dr. Felix's prepared statement follows:) OPENING STATEMENT BY DIRECTOR, NATIONAL INSTITUTE OF MENTAL HEALTH, PUBLIC HEALTH SERVICE, ON MENTAL HEALTH ACTIVITIES, PUBLIC HEALTH SERVICE Mr. Chairman and members of the committee, in a moment, I would like to discuss some important emerging patterns in the mental health field. But first, I will summarize the fiscal aspects of our budget as it is before you. For mental health activities in the fiscal year 1959 the budget proposal that is before you requests an appropriation of $37,697,000. This compares with $38,376,000 available for these same activities in fiscal year 1958. The apparent decrease is largely technical. The decrease is made up of $500,000 from grants for research projects due to the termination of the special 3-year study authorized by the Mental Health Study Act of 1955 (Public Law 182, 84th Cong.), and $179,000 from direct operations due chiefly to nonrecurring expenditures. Last year there were substantial savings in research grants partly due to the fact that the psychopharmacology program did not get started as fast as anticipated. This year it is anticipated that most of the funds appropriated for this purpose will be spent. The training-grant program has proceded as planned; the increase in 1958 of about $1,300,000 has been utilized to develop essential areas in the growing program for developing professionally trained manpower. The most notable change in the intramural program has been in the cooperative project with St. Elizabeths Hospital; the structural changes in the new facility are almost complete and the scientist who was recruited to direct this activity has taken charge of the laboratory and is proceeding ahead of schedule with his staffing. The request for mental health activities for fiscal year 1959 includes $11,902,000 for research grants, $546,000 for research fellowships, $13,300,000 for training grants, $4 million for grants to the States for mental health activities and other preventive and control services. It also includes $5,808,000 for intramural research, $591,000 for the review and approval of grants, $70,000 for in-service training activities, $1,221,000 for professional and technical assistance activities, including the work of the Psychopharmacology Service Center, and $259,000 for administration of the Institute. These funds are requested for expenses necessary to carry out the provisions of the Public Health Service Act as amended with respect to mental diseases, SOME EMERGING PATTERNS IN THE MENTAL HEALTH FIELD The experience of the National Institute of Mental Health over the last decade has greatly broadened its concept of the problems which are related to mental health. At the outset the major tasks were properly viewed as increasing the availability of adequate treatment, enlarging and improving the supply of trained mental health personnel, and mounting an expanded research program designed to solve many of the unanswered questions about mental illness. The Institute has made considerable progress in all of these areas. In addition, though, other problems have become identified as wholly or primarily within the mental health field. One such problem is the application of psychiatric and mental health approaches to the alleviation of persistent social problems such as delinquency, retardation, and drug addiction. Then, too, we have become increasingly concerned with the prevention of mental illness and the promotion of mental health as a positive asset of man, and initial steps were taken to explore how the basic agencies and organizations of the community tend to increase or decrease the probability that the individual can achieve and maintain a high degree of mental health. To illustrate further-the Institute recognized the need to know how the disasters and other extreme circumstances affect mental health and how the mental health status of people determines their ability to deal with these occurrences. Developments such as these, serving to enlarge the horizons of mental health as a field, have caused the Institute to give careful attention to the area of program development. During our early years, emergent problems were handled as they appeared, but more recently the Institute has developed systematic methods for determining program areas which will require attention if this Institute is to carry out its total mission. The major device has been intensive staff work designed to clarify the problem, followed by planned coordination of various Institute programs directed to different aspects of the problem, and buttressed by research designed to supply answers where lack of knowledge deterred adequate approaches and programing. The range of questions that have been studied in this way has been great. A large amount of work has been done on the problem of rehabilitating the mentally ill patient. Studies of the effect of the school and work situation on mental health have been initiated. The drug addict, juvenile delinquent, mentally retarded child, and the alcoholic have received attention. Major efforts, both intramural and extramural, have gone into the field of psychopharmacology. The psychological factors in accident causation and individual and group reaction to disasters have been studied. For the future there are additional problems that we know must be tackled, such as family disorganization and suicide. The results of these program development activities have been reflected in all of the operating programs of the Institute-research, training, and community services. The areas that have been illuminated by these problem-defining techniques appear diverse and in some cases almost unrelated, but in fact they fall into four well defined groupings: 1. The prevention or reduction of disability in pathologic or deviant populations (the delinquent, alcoholic, the clinically ill groups, especially the schizophrenic); 2. Processes affecting the mental health of large groups or entire communities (mental health education, child-rearing practices, aging); 3. Processes affecting the mental health of specific populations in organizational settings (schools and the work setting); 4. Mental health aspects of traumatic or stressful events in various populations (accidents, disasters, epidemics, etc.). The early work in these areas, plus the fact that the areas of program development do form a pattern, make the Institute feel that it has made much progress in bringing its continuing programs in research, training and community services to bear upon the problem of public mental health and that future orderly progress can be made to increase the contribution of mental health not only to the specific problems of illness but also to a large number of related problems. Some new understandings of the bases of normal and impaired human functioning There has been little agreement among people generally and even among research workers on such questions as whether human ability or disability is inherited or acquired, whether disordered behavior rests upon organic or life experience factors, and whether people grow old psychologically, physically, or both. The important fact is that hereditary influences and organic factors are properly viewed only as conditions of development. Except for the extreme case, they are not as limiting as previously thought. The organic factors are not presently subject to much change or manipulation in the individual; but the environmental factors are subject to control and have tremendous potential effects which are just now receiving recognition. It appears now that some meaningful things can be said about these problems. It is common knowledge that inherited characteristics and organic factors are involved in every aspect of a man's body, mind, or functioning. It has long been known, too, that as the individual develops and as his body changes, so does his behavior change. Today, however, it is becoming increasingly apparent that there is no simple 1-to-1 relationship between organic factors and the psychological functioning of the individual. Severe organic deficit is, of course, associated with badly impaired behavior and development. Short of such crucial defect, however, such factors as the situation in which one exists, the experiences he has, and the amount and kind of human interaction and support he has are of extreme importance to his phychological development. This conclusion comes from several areas of study. There was a time when intelligence was thought to be a fairly constant attribute of an individual. There were bright children, average children, and dull ones. It was thought they would remain what they were at first. It was then discovered that orphans who were presumed to be dull became much brighter when adopted into good and loving homes, while those who remained in the institutions appeared to get even more dull. These studies were almost ignored for a time. Later, other workers followed children from normal homes for their entire childhood. They found that the brigthest infant was not necessarily the brightest firstgrader. They found children who became progressively brighter and those who grew dull. It began to appear that what happened to the child affected his mental growth. He was born with a nervous system and an ability to learn from experience. How fast he learned and how much depended upon many |