APPENDICES

Minutes of the First Meeting Of the Joint Steering Committee
San Francisco, California, U.S.A. May 24-25, 1979

The meeting was called to order at 9:00 A.M. by Dr. Robert W. Miller, Director, Office of International Affairs, National Cancer Institute, and co-chairman of the Joint Steering Committee.
The attendees for the Japanese Committee were Dr. Haruo Sugano, Co-chairman of the Joint Steering Committee, Drs. Yuichi Yamamura, Yoshio Sakurai Takashi Sugimura, Mr. Kichimasa Soda, representing the JSPS, and Ms. Toshiko Takeuchi, JSPS. The U.S. was represented by Drs. Robert W. Miller, Stephen K. Carter, I. Bernard Weinstein, Robert R. Omata and Mrs. JoAnne Day. Unfortunately, Dr. William Terry was unable to attend due to his attendance at the meeting of the National Cancer Advisory Board, in Bethesda, Maryland.
Dr. Miller welcomed the Japanese members and mentioned that it has been a great change for him from substituting for Dr. Newell at the June 1978 meeting to becoming Co-chairman of the Joint Steering Committee. He expressed his hopes that this meeting would be as imaginative as possible in discussing the plans for the future and that different ideas could be fused to create a very dynamic program. He encouraged everyone to express opinions fully.
Although Dr. Guy R. Newell has resigned as Co-chairman, due to additional and pressing responsibilities, he strongly believed that the US-Japan Cooperative Cancer Research Program was one of the best bilateral programs sponsored by the NCI. Dr. Newell extended his best wishes to the Joint Steering Committee.
Mr. Soda, representing the Japan Society for the Promotion of Science, expressed the appreciation of the Japanese members and the JSPS for the arrangement of this meeting in San Francisco by the OIA Staff. He congratulated Dr. Miller on his appointment as Director, OIA. He also stated that Dr. Newell was also responsible for the success of the first five years of the Program through his leadership and support.
He then stated that this meeting was the first formal meeting of the Joint Steering Committee to develop plans and implement the Program for the second five years of the Program. He stated that JSPS is in full agreement on the new program structure in order to implement an efficient and flexible program. Thus far, the Program has been a great success and it has made a considerable impact on cancer research in both countries. He reported that during the first five years of the Program, 46 seminars, meetings and workshops were sponsored with over 1,000 total participants, and that 80 Japanese and 55 American scientists were selected as Exchange Scientists to engage in collaborative research activities. In addition, several research collaborations were instigated as corollary activities to the US-Japan Program and were not officially supported by Program funds. He reported that the JSPS budget has not been increased over last year’s funds, but he believed that quality and not quantity of activities was the measure of the progress of a successful cooperative program.
At the last meeting of the Committee in November 1978, the members congratulated Dr. Takashi Sugimura for being awarded the Imperial Medal for Culture by the Emperor of Japan. This time the Committee congratulated Dr. Miller for his new position as Director, Office of International Affairs, NCI, and also Dr. Omata for being awarded the PHS Meritorious Medal by the Surgeon General, Public Health Service.
Mr. Soda then thanked the NCI staff and Dr. Carter for making the meeting arrangements. He introduced Ms. Toshiko Takeuchi, who has succeeded Mrs. Yuko K. Furukawa on the US-Japan Program. She has spent several years in the U.S., most recently serving three years at the Japanese Embassy in Washington, D.C. He reported that Mrs. Furukawa just recently became the mother of a baby daughter. The Committee extended its collective congratulations and best wishes to Dr. and Mrs. Furukawa.
Dr. Omata announced that the U.S. side was inviting the Japanese members to an informal dinner at Fisherman’s Wharf. Mr. Soda invited the U.S. side to a luncheon to be held in old Chinatown in San Francisco.
Dr. Sugano, Co-chairman of the Joint Steering Committee, expressed his pleasure in co-charing this meeting with Dr. Miller and announced that beginning April 1, the newly structured US-Japan Program was effective.
He stated that the Chemotherapy Meeting was just completed in San Francisco and simultaneously the High Energy Radiation Therapy Meeting was held in Kyoto, Japan, May 22-23, 1979, both sponsored under the Cancer Treatment Program Area.
He expressed his hopes and beliefs that the second five years would stimulate increased cooperation and bring about many fruitful results. He stated that there has been mutual agreement on the new structure and basic policies and principles of the Program. The main purpose of this meeting was the following:

1. Discuss and confirm basic plans and policies;
   
2. Discuss program plans for the future; and
   
3. Discuss the basic strategy for the next five years.

Mr. Soda presented the latest version of the Program plan of the US-Japan Cooperative Cancer Research Program. (See pp. 93-95) The committee unanimously accepted the Program Plan.
Drs. Sugimura and Weinstein were asked to present the plans for the Etiology Program Area. They first reported that Cancer Prevention has become a major issue, not only nationally, but on an international basis. Dr. Weinstein proposed that Prevention might be duly considered as a topic for the biennial Interdisciplinary Program topic for 1980. Dr. Miller reported that Prevention has become a very popular topic recently and that the subject could have a great impact on the direction of cancer research in the near future; namely, the relevance of low-dose radiation effects and other environmental factors.
Dr. Sugimura reported that Prevention has become a topic of considerable discussion in Japan. The Radiation Effects Research Foundation (RERF, formerly the ABCC) has been interested in the subject. He also stated that it may be possible to obtain a supplemental increase of funds for research on prevention. Dr. Miller feels that U.S. activities in Prevention may be able to motivate Japan to increase research support.
Drs. Sugimura and Weinstein then named the persons who will act as advisors for the Etiology Program Area.

1. Epidemiology:
   Takeshi Hirayama, National Cancer Center Research Institute
   Robert W. Miller, National Cancer Institute
   
2. Chemical and Radiation Carcinogenesis:
   Shozo Takayama, Cancer Institute
   Harry B. Gelboin, National Cancer Institute
   
3. Viral Carcinogenesis:
   Hiroto Shimojo, Institute of Medical Science, University of Tokyo
   Hidesaburo Hanafusa, Rockefeller University
   Thomas Benjamin, Harvard University
   
4. Genetics:
   Susumu Nishimura, National Cancer Center Research Institute
   Warren Nichols, Institute for Medical Research, Camden, New Jersey

Then Dr. Sugimura reported that plans are being made to sponsor the following meetings under the Etiology Program Area:

1. Cellular and Molecular Biology:
   Dr. Yoji Ikawa, Cancer Institute, Tokyo
   Dr. Ira Pastan, NCI
   
2. Immunology:
   Dr. Toshiyuki Hamaoka, Osaka University
   Dr. Richard Hodes, NCI
   
3. Automated Cytology:
   Dr. Yoshio Tenjin, Kyoundo Hospital, Tokyo
   Dr. Myron Melamed, Memorial Sloan-Kettering Cancer Center, NY

Dr. Yamamura outlined the various research sub-areas which will be covered in the future under the Cancer Biology and Diagnosis Program Area.
I. Cellular and Molecular Biology
a. Alteration of cellular gene expression in transformation caused by known transforming sequence in oncoviruses.
b. Altered gene expression in neoplastic cells.
c. Cell to cell interaction in cancerous state.
d. Cancer phenotypes, especially those of cell membranes.
e. Interaction between cancer tissue and its surrounding tissues.
f. New experimental animal models.
The tentative subjects are interrelated and joint activities, including seminars and scientist exchange, will be related to these subjects.
II. Immunobiology
a. Antigenic nature of tumor cells.
b. Fundamental immunologic process in host response to tumor.
c. New approaches and preclinical trials in tumor immunotherapy
III. Diagnosis
a. Automated cytology
b. Flow-system monitoring of chemotherapy and immunotherapy.
The above programmatic sub-areas have been tentatively projected for the next five years, however, the subjects may change depending on the discussions between the principal advisors for each of the sub-areas.
The program activities for 1979 have been generally agreed upon as follow

For the exchange of scientists, the scientists involved will be related to the areas of collaborations sponsored under the Program Area. For the immediate future Dr. Masuo Obinata, Cancer Institute, Tokyo, Japan will be nominated for molecular biology to study with Dr. A. W. Neinhuis National Heart, Lung and Blood Institute, NIH, for 2 months. Others are being considered in Immunology and Diagnosis Areas.
Dr. Yamamura and his research group are preparing samples of Nocardia cell wall skeleton antigen to be sent to NCI for Phase I and II studies in immunotherapy. Preliminary studies in Japan show that the antigen is quite effective in treating lung cancer.
The Cancer Biology and Diagnosis Program will have exciting new areas to be covered in the future. Dr. Yamamura stated that good programming will be needed to explore the new area. Dr. Miller feels that the Steering Committee may be helpful in assisting in bringing up new areas Dr. Carter reported that clinical immunotherapy of lung cancer has raised new interest and should be considered for a meeting under Cancer Treatment.
The subject of automated cytology was discussed. It is possible that this subject may continue for the next five years, but it would depend on the advances to be made during the next year.
The subject of scientist exchange was discussed again. There are several other sources to support exchanges, namely the NIH Visiting Program Fulbright-Hays Program, Fogarty International Research Exchange Program and the JSPS Fellowships for foreign and Japanese scientists.
The meeting was recessed for lunch at the Great Eastern Restaurant, hosted by the JSPS. The meeting was reconvened after lunch.
Drs. Sakurai and Carter were asked to present the program developed for Cancer Treatment Program Area. The Cancer Treatment Area will organize seminars and symposiums based on chemotherapy, radiation therapy and immunotherapy, and orient the methods of treatment of cancers of the bladder, lung, breast and stomach. There are new opportunities to be explored in the treatment of other types of cancer not currently covered under the Program.
Dr. Sakurai reported that the Japanese working group has been selected as follows:

During 1979 three meetings have been planned, of which two were just completed:

This meeting will be a discussion on the multi-disciplinary approach to the treatment of lung cancer, in studying radiation therapy, chemotherapy and immunotherapy. There is new exciting data on the treatment of oat cells in lung cancer, which comprises 20% of the lung cancer cases. Also new data on the Nocardia cell wall skeleton vaccine show very interesting results.
At the last business meeting of the Cancer Treatment Program Area, tentative program plans were discussed. It was decided that the following meetings will be planned:

Dr. Carter reported that, in addition to the formal cooperation under the Program, the Joint Study of Gastric Cancer Treatment between the Northern California Oncology Group and the Japanese Group has made remarkable progress. The cooperative studies have been excellent. The preliminary data treatment results have been comparable and the survival rates have also been comparable. Although the total numbers have been limited, the studies show promises of effective treatment, particularly with chemotherapy after surgery. This study shows that joint cooperative studies can be worked out on comparable basis when they have been well-planned in advance. It is possible that a future study on breast cancer treatment will be effected.
Dr. Sugimura brought up the problem of the criteria used for treatment and cure in Japan. Dr. Sakurai stated that it is very important that such studies should use similar clinical protocols and criteria for staging and treatment results. Dr. Carter stated that chemotherapy has reached a point for evaluation over other types of therapy. Future work will be focused on the role of drugs in multidisciplinary treatment. He also stated that the development of new drugs in Japan has reached a stage where the methods for treatment are changing. He feels that the free enterprise system in Japan has made it possible to create competition and innovation in the development of new drugs. The criteria to measure response to drug treatment is being changed with new treatment methods. There is an increased intensity of interaction among the clinical researchers to exchange ideas and views.
Dr. Sugano brought up the subject of chemoprevention. Dr. Carter reported that 13-cis retinoic acid; a Vitamin A analogue, is being tested in a bladder atypia study. There is some data on the effective reversal of the precancerous process.
Dr. Carter stated that clinical study on gastric cancer has shown there is comparability of clinical results and this can be a model for other clinical studies. At present, the total numbers are not adequate. More data will be needed in the future to evaluate the results. Dr. Sakurai anticipated the development of more cooperation in chemotherapy studies in the future. Studies on side effects, as well as qualitative and quantitative results of drug therapy will be necessary in the future. Dr. Carter stated the biostatistical analyses in clinical studies are very important and that there is need for further advances in the use of biostatistics.
Dr. Sakurai believes that long-term scientist exchanges of young Japanese scientists may not be necessary in their Program Area but exchanges should be concentrated on specific subject areas and clinical trials. He feels that clinical trials should be continued since they will help remedy the short-fall in methodology in medical oncology in Japan. He would like to see more young Japanese specialists study the American procedure in treatment and data analysis of clinical trials. Both Drs. Carter and Miller agreed that even in the U.S. there is a lack of good clinical epidemiologists studying and analyzing clinical trials.
At present there is no formal certification of oncologists in Japan Currently there are residency training programs in oncology at the National Cancer Center Hospital in Tokyo and at the Institute of Adult Diseases in Osaka.
Dr. Sugano stated that the Interdisciplinary Program Area has the responsibility to coordinate the whole US-Japan Cancer Program and to provide support for new or special areas of interest. In addition, meetings on multi-disciplinary aspects of organ site and the biennial large conferences will be sponsored by this Program Area. The advice of the Joint Steering Committee will be asked to formulate the programs for this area.
Dr. Miller stated that the Joint Steering Committee members should suggest new areas of interest as well as make recommendations for special topics or subjects for the biennial conference. New advances in cancer research and special topics with emphasis on the US-Japan Cancer Program and inter-disciplinary subjects should be stressed. The subject of nutrition and cancer was brought up. It was decided that there have been few new developments in the nutrition field and a meeting in the near future is not necessary. It was agreed that a conference on “Recent Advances and New Approaches to Cancer Research” be sponsored in Japan during the second week of June 1980, possibly in the Kansai area. The Joint Steering Committee will also be meeting either prior to and/or after the conference.
It was agreed that in the future annual summary reports will be prepared by the Program Area Coordinators and be published. A format for the reports should be devised for consistency of the format.
Mr. Soda reported that the JSPS has formed an Advisory Committee for the US-Japan Cooperative Cancer Research Program to provide overview and policy recommendations to the JSPS.
The meeting was adjourned at 5:00 PM and it was agreed that the Committee would meet at 9:00 AM on Friday, May 25th.
The NCI hosted a dinner for the Japanese members of the Joint Steering Committee at Fisherman’s Wharf.
The meeting was called to order by the Chairmen: Dr. Sugano and Dr. Miller at 9:00 AM.
Early discussion was centered on time and place of next Joint Steering Committee Meeting.
It was agreed to hold the biennial conference in the Kansai area of Japan, either in Nara and Osaka. The first day would be devoted to the Joint Steering Committee Meeting and on the second and third days the scientific meeting will be held. It was generally agreed that 45 minutes be allocated for each presentation, with three per session i.e., 30 minutes per presentation and 15 minutes for discussion. Dr. Sugimura suggested that a short follow-up meeting of the Joint Steering Committee be held on the fourth day to discuss any new items of interest brought up by the scientific meeting. The Program Coordinators will agree on the subject to be discussed. Dr. Weinstein suggested that a book of abstracts of the presentations be prepared for public distribution.
Dr. Miller brought up the subject of poor quality of slides and expressed hope that the slides could be prepared at one place (perhaps by NIH) to avoid poor quality of slides.
Dr. Weinstein mentioned that the American Association for Cancer Research (AACR) has guidelines for slides. He stressed the need for the cooperation of all speakers in the preparation of good slides.
Dr. Sugano and Mr. Soda discussed support from the Japanese side for the large scientific meeting. It was thought that the JSPS and the Japanese Cancer Association could provide support.
Dr. Miller suggested that a summary of the meeting be published. Dr. Weinstein suggested the possibility of also publishing a report of the meeting in Cancer Research, of which Dr. Peter McGee is the Editor. Dr. Miller suggested that abstracts be provided to participants and interested individuals in advance of the meeting.
The question was raised if the meeting should be published in Japanese as well as English. Dr. Sugimura stated that it was unnecessary to publish in Japanese.
Mr. Soda stated that it might be appropriate to have some time for general discussions after the scientific session. The group felt that this discussion could be held after the large meeting at the continuation meeting of the Steering Committee.
The subject of cancer prevention was then brought up. Dr. Weinstein stated that current NCI plans reflect the trends and pressures from the public. Dr. Miller stated that Dr. Upton will create a new entity-Division of Cancer Prevention. The Division of Cancer Control will be eliminated and replaced by the Division of Cancer Resources, Centers and Community Programs. This will include cancer centers and organ site programs.
Dr. Weinstein stated that there is considerable pressure from Congress to emphasize Cancer Prevention.
Dr. Sugimura stated that concern about Prevention was world-wide. He felt that with the great emphasis on Prevention, perhaps more funds could be appropriated for the Program.
Dr. Weinstein brought up the recent problems with dumping of hazardous wastes, regulatory procedures, etc. He stated that this new area of prevention will deal with many entirely new problems and possible solutions, such as disposal of chemicals, behavior modification related to smoking, etc. Dr. Miller reiterated that what Dr. Weinstein was saying was that with the new field of Prevention becoming more visable and important, the Interdisciplinary Program Area will have to cover this area as well.
Dr. Yamamura brought up the subject of immunopotentiating agents and problems of cancer with fabric and other industrial workers. Dr. Miller brought up the subject of low-dose radiation. He stated that there are three examples of low-dose radiation having effects on cancer:
(1)Utah Studies
(2) Military personnel who watched nuclear explosion tests;
(3) Nuclear shipyard workers
All of these three groups developed leukemia more often than the normal population. Emphasis in the U.S. has now been directed on research on radiation effects and more funds will be channeled into the basic research in the future.
Dr. Sugimura suggested that careful investigations should be made into the fate of survivors of Hiroshima and Nagasaki, but that these meetings should be kept low-key. He felt that it would not be a good idea to publicize the studies, as it would evoke strong reactions to the atomic bombings and radiation. He also stated that large programs on screening for stomach cancer are on-going.
Dr. Miller stated that with the focus on radiation now, perhaps less importance is being placed on chemical carcinogenesis, which should not be the case.
Dr. Yamamura brought up the studies and use of cytoxin, and the possible role in causing secondary cancers.
Dr. Sugano stated that in Nagasaki there is increased incidence of leukemia, breast cancer and stomach cancer.
Dr. Weinstein suggested that in the future a meeting on prevention would be fruitful.
Dr. Miller mentioned xeroderma pigmentosum, as an example, in which clinical observations in man lead to basic research. Host susceptibility to tumors is a very important subject, which has not been fully investigated.
Dr. Weinstein stated that once you tell people that maybe 80% of cancers are preventable, they will want to know how to prevent them. Physicians will need to know how to interpret data and determine implications. He then asked if chemical dumps posed a problem in Japan also. Dr. Sugimura stated that there were many problems associated with chemical dumps in Japan and that he felt that this area should be explored under the Program.
Dr. Miller stated that the National Academy of Sciences has a committee on chemical disasters, which is studying the problem. Also, that there is some surveillance going on after a PCB accident. Studies are indicating that drugs are metabolized at different rates. Also, the same problems are associated with PBB’S.
Dr. Weinstein stated that they are planning a conference on “Biochemical Epidemiology” which would focus on laboratory methodologies, markers, blood metabolism and immunological markers. He stated that a future conference could be planned on chemical-viral interactions.
Dr. Miller closed by stating that this meeting had been very successful, with a variety of thoughts being expressed. He felt that this was due to the flexible structure of the meeting.
He thanked Ms. Takeuchi and Mrs. Day, Dr. Omata, Mr. Soda, Dr. Sugano and all the participants for sharing their valuable time and knowledge.
Dr. Sugano agreed, saying that he was pleased to attend the first meeting of the second five-year Program. He felt that the meeting was extremely successful. He was pleased that the new Chairman of the U.S. side was an old friend, and the Japanese side was pleased to have him involved in the Program in this new capacity.
Mr. Soda expressed the feeling that administrators should serve the Programs by trying to keep the procedural requirements at a minimum.
Dr. Sugano expressed his sincere thanks to Dr. Guy R. Newell, who was Chairman of the Program for the first five years.
The meeting was adjourned at 10:45 A.M., Friday, May 25, 1979.