the thoughts which have been expressed by some of the previous panel' members and ask Dr. G. B. Mider to indicate some of the advances in research being carried on at the National Cancer Institute, in order that this program may be rounded. Dr. Mider.

STATEMENT OF DR. G. BURROUGHS MIDER, ASSOCIATE DIRECTOR IN CHARGE OF RESEARCH AT THE NATIONAL CANCER INSTITUTE

Dr. MIDER. Mr. Chairman, may I enter a prepared statement of the work of the National Cancer Institute?

The CHAIRMAN. Without objection, it is so ordered. (The statement referred to follows:)

CANCER

Prepared by the National Caucer Institute, National Institutes of Health, Public Health Service, United States Department of Health, Education, and Welfare

REPORT OF THE NATIONAL CANCER INSTITUTE ON THE CANCER PROBLEM

The control of cancer requires that the medical, social, and economic impact of neoplastic disease be minimized through preventive measures, effective treatment, or both. Alleviation of pain and the increase of an individual's useful years of life represent tangible and significant advances toward the goal of complete eradication.

All of these must be tied together to subjugate cancer: Knowledge, definition and broadening of areas of responsibility; stimulation and support of cooperative enterprises among clinical, laboratory, preventive medicine, social and other interested disciplines; employment of investigative techniques which are increasingly directed or applied; and the initiation and supervision of specfic field studies and investigation.

First, much more must be known of the causes, diagnosis, treatment, and prevention of malignant neoplasm. From the standpoint both of research and disease control, cancer may be considered as a group of diseases rather than as a single entity. Each of these diseases has as a common denominator the loss of the ability of the cells to achieve a normal life cycle. Starting from this general base, hundreds of highly skilled workers are devoting their life's work and millions of dollars are being expended annually toward a solution. The following discussion merely highlights some of the present difficulties that will most certainly require the contributions of additional hundreds of scientists and the expenditure of many millions of dollars.

MAGNITUDE OF THE CANCER PROBLEM

Most people have lost a close friend, a relative or even a member of the immediate family from cancer. This becomes understandable when the annual toll from this disease is considered on a nationwide basis. Cancer is the second leading cause of death, ranking next to cardiovascular diseases in this respect. It is now the stated cause of approximately 1 out of every 7 deaths in the United States, with more than 200,000 deaths occurring from cancer each year-the preliminary figure for 1952 was 224,130.1 The importance of cancer as a cause of death is not confined to certain age periods but extends across the entire life span. Between 5 to 14 and 35 to 74 years it is the second leading cause and only at ages under 5 and over 85 years does it drop below third place when the causes of death are ranked in importance.

Because of the lack of information from other sources, mortality data have been relied upon in the past to describe the scope of the cancer problem. Important as they are, death statistics by themselves cannot define the problem adequately. As treatment becomes increasingly more effective, the curable types of cancer appear less frequently in mortality records. Furthermore, the medical certification of death states only the immediate and contributory causes of death

National Office of Vital Statistics, Monthly Vital Satistics Report, vol. 1, No. 13, July 21, 1953.

and the number of persons dying with cancer is inevitably understated. This can occur because the certifying physician may not know or does not deem it necessary to indicate that cancer was present, or because death was obviously due to some cause unconnected with the presence of a cancer.

The approach adopted by the National Cancer Institute to secure data on the extent of illness from cancer is to canvass all the diagnostic sources within a -community-hospitals, clinics, laboratories, practicing physicians-and to secure lists of all persons coming to diagnosis or currently under treatment, so that an unduplicated count of persons ill with the disease may be prepared. Ten urban areas were surveyed in 1937-39 and resurveyed in 1947 and 1948. To insure more complete coverage, data on cancer deaths were obtained at the same time from city and State offices of vital statistics. The mortality records provided information on a substantial number of cancer cases not reported by other sources. In the 10 cities surveyed in 1947 and 1948, the results indicated that cancer was being diagnosed at an annual rate of 319 new cases per 100,000 population and that 430 of every 100,000 persons were under treatment for the disease sometime during the year. Since the age distribution of these city populations is somewhat younger than for the country as a whole, rates for specific age categories were computed and applied to the United States population at each age for the purpose of making national estimates. Based on the findings of the 10-city morbidity surveys, the incidence (new cases per 100,000 population) for the United States (1950) was estimated to be 328 and the prevalence rate (cases under treatment during the year per 100,000 population) 441.

The age distribution of the population changes with time. If prevailing death rates at each age continue, in 1975 some 1,008,000 persons will be under treatment for cancer and 326,000 will die.

Unless the cancer death rate for older people can be drastically cut, the number of persons affected by cancer will increase by more than 50 percent during the next 25 years because a larger proportion of the population is living into the upper age brackets.

Age distribution of diagnosed cancer cases

The emphasis on the increased risk of developing cancer at the older ages should not conceal the fact that a very substantial number of cases are diagnosed among children and young adults. In the recent morbidity surveys 15.6 percent of all cancer cases diagnosed during the study year were persons under 45 years. Probability of developing cancer

Sobering as they are, annual rates for incidence, prevalence, or mortality do not adequately describe the total cancer problem. Cancer investigators have to consider the risk of the disease developing over intervals as long as 10 or 20 years. Unless there is a reduction in the proportion of people who get cancer, of 100 people born during 1950, 32 will develop cancer at some time during their lives; cancer would develop in 3 before age 45, in 14 before age 65, and in 23 before age 75.

If cancer illness rates are not cut, approximately 50 million people now alive are going to have cancer and 25 million will die of it.

The lifetime probabilities for developing cancer of specific sites vary greatly From birth to age 65, 1 in every 12 women will have cancer of the genital organs or breast. For both sexes up to age 65, 1 in 22 will have cancer of the digestive system; 1 in 55, skin cancer; 1 in 83, cancer of the respiratory system; and 1 in 14, cancer of the urinary organs; 1 man in 142 will develop cancer of the prostate. The high incidence rate after age 65 for cancer of the digestive system makes it outrank cancer of the female genital organs and breast in overall lifetime probability.

Under current conditions, 16 of every 100 persons born can be expected to die from cancer; 1 person can be expected to die by age 45, 6 at age 65, and 11 at 75; 1 person in 7 now age 45 or older will die of cancer.

Hospitalization

Some 711,000 cancer patients will receive medical care in the United States during 1953. Data collected by the National Cancer Institute indicate that 62.1 percent of this total, or 441,530 cancer patients, can be expected to occupy hospital beds for an average of 27 days; 1 out of every 14 general hospital beds is occupied by a cancer patient. This proportion has increased

2 Atlanta, Birmingham, Dallas, Denver, Detroit, Chicago, New Orleans, Philadelphia, Pittsburgh, San Francisco.

steadily since 1900 and accounts, in part, for the increasing need for hospitals despite the fact that over 102,000 beds have been added since 1946 as the result of the Hill-Burton program.

Available evidence indicates that cancer patients are receiving better medical care than they did 10 or 15 years ago. The proportion of cancer cases receiving medical care in a hospital (or a hospital clinic) may be taken as a rough index of quality of medical supervision. Of all cancer cases reported in the 1937 series of surveys by the National Cancer Institute, about a third (32 percent) did not receive medical care in hospitals. Even in 1947, more than a quarter (27 percent) did not receive hospital medical care.

Microscopic examination of tissue for verification of clinical diagnoses of cancer is accepted as necessary to insure accurate diagnosis and its frequency serves as another index of quality of medical care. Even in 1947, almost a quarter of the cases (23 percent) were not microscopically confirmed.

Economic loss

During 1953 about 530,000 new cases of cancer will be diagnosed. Probably three-fourths of the potential economic production of these cancer victims will be lost to society. Taking the age distribution of new cases of cancer into account, and counting as lost only those years that an individual may be considered as productive, the discovery of 530,000 cancer cases represents a loss of 3.5 million man-years of work.

Current estimates fix the average annual contribution per member of the labor force (age 18-65) to the gross national product at $3,500. Thus, the cases of cancer diagnosed in just 1 year (1953) will cost society $12 billion in lost goods and services. This includes the cost of medical care and the value of the potential economic productivity of persons caring for cancer patients.

Disruption of families

Mortality statistics and loss of man-years due to illness from cancer do not show specifically the impact of this disease on the basic unit of our society— the family. Illness of any kind may be financially upsetting to an ordinarily self-sustaining family. A terminal illness involving long-term, expensive treatment is usually overwhelming. When the cancer patient has been the breadwinner, cancer is a total family catastrophe.

It is difficult, if not impossible, to assess the effects of the loss of status or self-respect when a family is forced to accept relief which they had never previously needed. How can one measure the long-term effects on children whose mother must assume a wage-earning role because of the father's illness? Conversely, what yardstick can be applied to the difficulties which must be faced by a father of small children when their mother is ill with cancer? One-third of all cases of cancer in women occur between the ages of 35 and 55, when women are most likely to have teen-age children. Nearly one-fourth of all cases of cancer in men occur at these ages.

These effects of cancer have been inadequately studied. Little quantitative information is available. Economic difficulties are most likely to bring family problems to the attention of social agencies. In dealing with this compelling factor caseworkers have uncovered the more personal attitudes and reactions— fears, anxieties, reactions of guilt, and so on-which are frequently even more crippling to the family as a whole than the added fiscal burdens. This area of research will be of ever-increasing importance so long as the incidence of cancer continues to rise and definitive cure or prevention of the disease remain a problem.

So far this discussion has centered around the cancer patient already in or approaching the terminal stages of the disease. The other side of the picture concerns the cancer patient who has been made well enough to work. Quantitative data on this aspect of cancer illness are scanty, and what is known is dismal. Most industries refuse to employ individuals who have had cancer because of the increased risk of compensable illness. New opportunities for creative or productive employment are difficult to find for many cancer patients, particularly males.

Thus, there is nearly a total socioeconomic loss to the community in the case of male cancer patients, and a substantial one with female patients, even when they have survived their initial course of treatment for the disease. This difference between posttreatment experience of males and females is consistent with the more general statistical fact that while the rate of onset of new cases of cancer is practically equal for males and for females, the mortality rate

from cancer in males is now higher than in females. The reasons for this latter fact are not clear and systematic exploration in this field is indicated. Most people know what happens to a person with advanced cancer. The medical, social, and economic effects of the late stages of cancer tend to perpetuate delays in diagnosis. Dread of pain and of physical or economic dependency has been found to be an important factor influencing people to delay in seeking medical advice when cancer should be suspected. This results in

an ever-widening circle of loss to the community and to the Nation.

FUNDS ADMINISTERED THROUGH THE NATIONAL CANCER INSTITUTE The National Cancer Institute was established in 1937 and received as its first appropriation $400,000 for fiscal year 1938. For the next 8 years appropriations remained at approximately the same level. After World War II when the necessity for diversion of funds to military needs had lessened and the Institute research program had become more firmly established, the increasing nationwide concern over the cancer problem resulted in an appropriation of $1,772,000 for fiscal year 1947. This relatively large increase over former years was to provide not only for expansion of the Institute's own program of research but also to provide additional support in the form of grants to cancer scientists in no governmental laboratories.

The beginning of the present scope of operations was, however, in 1948, when $14,500,000 was appropriated primarily to broaden and increase the granting program including for the first time grants for the construction of additional nongovernmental research facilities. Funds for construction were provided each year thereafter until 1953. The total appropriations for the National Cancer Institute for the intervening years were $14 million for 1949; $18,900,000 for 1950; $20,686,000 for 1951, and $19,500,000 for 1952. The provision of additional facilities increased the demand for support of cancer research and as the construction program began to taper off, funds available for other types of grants were increased. In 1953, therefore, although no funds were provided for construction grants $17,887,000 was appropriated.

The appropriation for the present fiscal year is $20,237,000 of which slightly more than 70 percent is appropriated for grants, almost 25 percent for research at the National Cancer Institute, and approximately 5 percent for auxiliary programs.

Of the $14,324,000 available for extramural activities, i. e., grant programs, $8,469,000 or approximately 60 percent is budgeted for project grants to scientists engaged in cancer research. In addition, $750,000 is budgeted for research fellowships, a program established to provide experience and training opportunities in research for promising young scientists. The remainder of the funds budgeted for extramural activities are devoted to cancer-teaching grants to medical and dental schools ($2,355,000); cancer-control grants to States ($2,250,000); and to training grants ($500,000), the latter utilized to provide special cancer training and experience to practicing physicians. The remainder of the National Cancer Institute appropriation, $5,913,000, is budgeted for operations carried out directly by the Institute. Five million thirty-one thousand and two hundred dollars of these direct operations funds are budgeted for the support of the laboratory and clinical research carried on at the National Institutes of Health, and $329,000 or approximately 1.6 percent of the total budget is for administration. Also, $393,000 is available for a technical and professional service engaged in interpreting the results of cancer research and in finding the direct practical application of these results to the cancer problem in order to benefit the general public.

The proportions budgeted for the various activities of the National Cancer Institute vary somewhat from year to year. The proportions set forth above, for the present fiscal year, however, are considered typical. From this it can be seen that combining extramural and intramural research activities 70 percent of appropriated funds are devoted to cancer research and approximately 29 percent to closely related activities serving to assist research and to capitalize on research results.

RESEARCH FOR FINDING IMPROVED METHODS FOR CONTROL OF CANCER

Most improvements in the care of the cancer patient will result from research. Many scientific specialties have contributed significantly to progress in cancer research and will continue to do so. Such a broad attack may seem diffuse to those not acquainted with the field, but experience has shown that

advances in the study of diseased states must in large measure await the avail ability of information obtained from investigations that seem to have little or no direct application to everyday problems. The point is often made, and can be substantiated from history, that practical applications of scientific facts and principles, such as inventions, are inevitable consequences of progress in amassing accurate information. It is for these reasons that research in several disciplines of science must form an integral part of cancer research. Many of these studies do not appear to be as spectacular as some of those made on cancer present in the patient, but it is important to keep in mind that if the supply of fundamental information is not constantly replenished, practical, tangible results for the patient will be all the more slow in coming. Many of the results which the cancer research worker considers highly significant never receive emphasis in the reading material presented to the public. A truly great amount of progress has been made in the last decade in this area of research. We have a much more thorough understanding of the nature, initiation, diagnosis, cure, palliation, and prevention of cancer than ever before.

Before discussing some of the most significant recent advances in these areas of cancer research, a significant accomplishment in general biochemistry of great importance to the cancer problem will be briefly mentioned as an example taken from an orthodox discipline of science. The availability of isotopes has provided a unique tool for biological and medical research. By using the isotope as a label in particular compounds it has become possible to follow what happens to various portions of ingested materials (food, drugs, oxygen, water, etc.) as well as breakdown products (including waste materials) derived from the tissues. This can now be done without radically altering the functioning of the living organism. Only a small amount of the isotope is necessary and the organism cannot distinguish between a compound containing an isotopic label and one not containing such a label. These studies, impossible before isotopes became available, have brought about a whole new concept of the living organism. Formerly, the structures of the adult body were considered to be static. Now, from these investigations with isotopes, it is known that actually the individual chemical components that make up the tissues are in a continual state of flux. This dynamic viewpoint of normal tissues has, naturally, led to a new viewpoint of cancer. Indeed, a number of cancer investigations employing isotopes have revealed certain important differences between cancer and normal tissue. Recently the isotope technique has been extended to allow a measurement of the rates of fundamental tissue processes in the intact experimental subject. This extension offers a new approach in the attack on cancer and other diseases since it is possible to measure in living tissue in a dynamic way differences which cannot be detected by the older ordinary analytical methods. Such fundamental studies both in normal and in cancer-bearing subjects must continue to form an integral part of cancer research, for cancer is, after all, a part of the phenomena that make organisms live.

Studies on the initiation of cancer

A summary of an extremely large amount of long and laborious work, indicating several significant advances, can be given by a listing of certain basic principles relating to the causation of cancer which have been affirmed and reaffirmed in each of several species studied, including man:

1. A wide variety of apparently unrelated agents-chemical compounds produced synthetically, naturally occurring compounds, radiations, and biologic entities can elicit cancer.

2. Most of the potent agents will evoke cancer in only a fraction of the population studied.

3. The cancers that follow application of a powerful cancer-producing agent develop after a long period of apparent well-being which may be measured in weeks or months in laboratory animals but is probably a matter of years in man. 4. The advent of cancer need not be preceded by any constant, predictable, structural change in the tissue that is destined to become cancerous, at least by the methods of detection now available. In some specific cases, however, such changes can be detected.

5. Quantitative relationships between the character and intensity of some stimuli capable of producing cancer on the one hand, and the responses of laboratory animals on the other, have been defined.

Experience in studying those persons whose cancers arise as the result of accidental occupational or industrial exposure to carcinogenic hazards substantiates the validity of these generalizations. Additional confirmation is