POLIOMYELITIS CONTROL

"The transformation of the relatively uncommon 'infantile paralysis' of the 19th century into 'epidemic poliomyelitis' of almost worldwide distribution presents today one of the most formidable public health problems." These words from the 1953 report of the World Health Organization's Expert Committee on Poliomyelitis summed up the gravity of the situation.

Since that time many important advances in the knowledge of poliomyelitis have been achieved. The discovery by Dr. John Enders and his colleagues (Nobel Prize winner, 1954) that poliomyelitis virus would multiply in tissue cultures of non-neural human cells led directly to the development of a poliomyelitis vaccine by Dr. Jonas Salk and his associates.

In 1954 a large-scale field trial of the Salk vaccine was undertaken in the United States under carefully controlled conditions, and in April 1955 it was announced that the vaccine was safe and effective. By late fall of that year, despite some initial difficulties, the vaccine was successfully used on a large scale in the United States, Canada, and Denmark, and on a smaller scale in Germany and South Africa.

The experience gained in these countries obviously could be of use in other countries. To facilitate an international exchange of views on poliomyelitis control, the World Health Organization's Expert Committee on Poliomyelitis was convened in July, 1957.

In June, 1958, experts responsible for biologics control in ten countries met at the invitation of the World Health Organization, to draft international recommendations for poliomyelitis vaccine requirements. Those attending were Dr. Roderick Murray, U. S. A.; Dr. O. Bonin, Germany; Dr. D. G. Evans, United Kingdom; Professor S. Gard, Sweden; Dr. J. H. S. Gear, South Africa; Dr. Á. Lafontaine, Belgium; Dr. P. Lepine, France; Dr. H. von Magnus, Denmark; Dr. G. Penso, Italy; and Dr. V. Soloviev, U. S. S. R. The recommendations developed by the group were based closely on the United States' experience with poliomyelitis vaccine.

The continued successful use of poliomyelitis vaccine, as well as future developments in the field, may depend on knowledge of the various poliomyelitis viruses prevalent throughout the world and of other viruses causing similar clinical syndromes. The cooperation of national laboratories with World Health Organization regional poliomyelitis laboratories will facilitate the collection, interchange, and study of poliomyelitis viruses, and the exchange for study of viruses which may be responsible for clinical diseases resembling poliomyelitis.

INTERNATIONAL BIOLOGICAL STANDARDIZATION

There are compelling reasons why biological standards should be uniform throughout the world. Experience has shown the difficulties in which physicians, public health services, and manufacturers alike can be involved through the existence of a variety of different units expressing the potency of one and the same drug.

The decision to study the problem of biological standardization internationally was made by the League of Nations' Health Committee at its second session in Geneva, in 1921. Since World War II, the work has been carried forward by the World Health Organization's Section on Biological Standards.

The method of work today is founded entirely on international cooperation, just as it was in the beginning. A national control center is designated in each country to take charge of the international standards and equivalent national standards. The Statens Seruminstitut in Copenhagen is responsible for storage and distribution of international standards for vaccines and antisera. Pharmaceutical substances are maintained at the Medical Research Council's Department of Biological Standards in London.

Last year the World Health Organization initiated a program for the development of international recommended requirements for both the manufacture and the control of biological substances. Adoption of these requirements by national control authorities would promote improvement and greater uniformity in biological products, and would permit free exchange of such substances between nations in times of emergency. So far, recommended requirements have been drafted for poliomyelitis vaccine, yellow fever vaccine, and cholera vaccine. None have as yet been officially adopted.

SOME MAJOR PRODUCERS, CONTROL CENTERS, AND INVESTIGATORS OF BIOLOGICAL PRODUCTS THROUGHOUT THE WORLD

Pasteur Institute, Dakar, French West Africa

The South African Institute for Medical Research, Johannesburg, Union of South Africa

The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

Oswaldo Cruz Institute, Rio de Janeiro, Brazil

Butantan Institute, Sao Paulo, Brazil

Medical Research Institute, Colombo, Ceylon

Statens Seruminstitut, Copenhagen, Denmark

Lister Institute of Preventive Medicine, London, England

National Institute for Medical Research, Mill Hill, London, England Pasteur Institute, Paris, France

Paul-Ehrlich-Institute, Frankfurt-on-Main, Germany

Haffkine Institute, Bombay, India

Pasteur Institute of Southern India, Coonoor, India

Central Research Institute, Kasauli, India

Pasteur Institute, Bandung, Indonesia

Pasteur Institute of Iran, Teheran, Iran

Laboratory of Microbiology, Instituto Superiore di Sanita, Rome, Italy

National Institute of Health, Tokyo, Japan

West African Council for Medical Research Laboratories, Yaba, Lagos, Nigeria

State Institute of Hygiene, Warsaw, Poland

Karolinska Institute, Stockholm, Sweden

State Bacteriological Laboratory, Stockholm, Sweden

Queen Saovabha Memorial Institute, Bangkok, Thailand

Biologics Control Division, Central Institute of Hygiene, Ankara, Turkey

Division of Biologics Standards, National Institutes of Health, Bethesda, Maryland, U. S. A.

Institute of Epidemiology and Microbiology, Moscow, U. S. S. R. Moscow Institute for Poliomyelitis Prophylactics, Moscow, U.S. S. R.

SIGNIFICANCE OF FOREIGN CONTRIBUTIONS TO PRES

ENT KNOWLEDGE IN THE FIELD OF CANCER

The study of cancer is as old as medicine itself. Some of the earliest written records of human knowledge reveal that men of science and learning were vitally concerned with the cause and treatment of malignant tumors. The accumulation of knowledge about cancer, however, has not been a continuous process. For many centuries, particularly during the Middle Ages, little of value was learned about the nature of cancer, its cause, and treatment. The era of modern cancer research really began less than 200 years ago, at the close of the 18th century.

The period of the 19th and 20th centuries witnessed many fundamental changes in cancer research, as in all of medical science. Great strides were taken in the identification and classification of cancer, knowledge of cancer causation, and treatment. During this period, cancer research became experimental in nature, laboratory animals came into use, the systematic study of disease pathology-was born and enlarged, and the development of the microscope and other valuable research tools permitted scientists to gain knowledge about the basic unit of life, the cell.

Cancer research continues to expand fruitfully through the contribution of investigators in many countries throughout the world. The United States has made the largest contribution in money, facilities, and trained personnel; but future knowledge and advances are also dependent on the work of scientists in other countries.

In this report the principal discoveries and advances in cancer research, both ancient and modern, are summarized. Although the signifiance of foreign contributions is emphasized here, the work of American scientists in the development of modern cancer research cannot be omitted. The report is concluded with a brief account of the currently important fields of cancer research abroad.

ANCIENT CANCER RESEARCH

Cancer Recognized by Ancient Peoples.-The ancient Indian epic, the Ramayana, 2000 B. C., describes a disease resembling cancer. Five hundred years later, the author of the Ebers Papyrus in Egypt referred to cancerous growths and their treatment.

Ancient Forms of Treatment.-The surgical removal of malignant tumors was widely practiced by Indian physicians 4,000 years ago. Almost equally long ago, Egyptian physicians used an ointment of arsenic and vinegar in treating external cancers. These two forms of treatment were utilized through the ages; and one of them, surgery, remains a proved method of treatment and curing cancer. Description and Classification of Cancer. Hippocrates, who lived in the fifth century B. C. in Greece, first recognized benign and malignant tumors, a major advance over the earlier Indian and Egyptian

concept that all swellings were cancerous. More than ten centuries later, Paul of Aegina in the seventh century A. D. stated that cancer could arise in any external or internal part of the body, a concept well recognized today.

Early Theories on the Causation of Cancer.-The methods available to ancient investigators seriously hampered their work in the area of cancer causation and led to many unproductive theories. For example, Galen, a Greek of the second century A. D., considered cancer to be a manifestation of the individual's constitution, and this belief persisted almost to modern times. But Galen was nonetheless a skilled investigator who recognized that a primary cancer could give rise to secondary tumors and that the disease must be diagnosed at the earliest possible time.

MODERN CANCER RESEARCH

Percival Pott: The First Modern Cancer Research Scientist.Perhaps the first accurate description of tumors resulting from a specific, known cause occurred in 1775 when Percival Pott, the English surgeon, related scrotal cancer in chimney sweeps to prolonged exposure of these men to soot.

Cancer: A Disease of Cells.-Marie-Francois-Xavier Bichat, a French anatomist who died in 1802 at the age of 31, recognized that tumors must be composed of cells. Bichat's work was purely theoretical, because his investigations were conducted without the aid of a microscope. Johannes Müller, a Berlin scientist, published in 1838 the first extensive microscopic study of diseased tissue and definitely established the part of the cell in tumors. His classification of tumors was the first to be based on the appearance of the tumor cells.

Virchow and the Rise of Pathology.-Müller's most famous pupil was Rudolph Virchow who sensed the importance of the microscopic approach to pathology. His book, "Cellular Pathology," published in 1858, is one of the most important works in the history of medicine. Virchow's work made possible the accurate diagnosis of cancer by tissue examination.

Chronic Irritation as a Cause of Cancer.-Virchow suggested that some cancer develops as a result of chronic irritation, a theory acceptable today with modification. In 1915 two Japanese scientists, Yamagiwa and Ichikawa, successfully induced tumors on the ears of rabbits after prolonged and repeated applications of coal tar. This was the first case of the production of experimental tumors by the application of a carcinogen (cancer-producing substance), and it lent support to Virchow's chronic irritation theory. The era of experimental chemical carcinogenesis began in 1926 when E. L. Kennaway and his group at the University of London extracted 3,4-benzpyrene, a well known carcinogen, from coal tar.

Systematic Cancer Research in Animals Becomes Possible.-A relatively obscure Russian veterinarian, M. A. Novinsky, first successfully transplanted a tumor from one dog to another. This was accomplished in 1876. Then, at the turn of the century, Carl Jensen, in Denmark, developed a transplantable tumor in rodents, which made it possible for research scientists to study cancer in relatively cheap, small, fast-breeding animals.

Continued Improvement in Cancer Surgery.-Christian Billroth (1829-1894), an Austrian surgeon, was the founder of modern abdominal surgery. His work constituted a new departure in the surgical treatment of internal cancer.

X-Ray and Radium.-Near the end of the 19th century, a new and powerful weapon against cancer was discovered by European scientists. In 1895, the German physicist, Wilhelm Conrad Roentgen, reported the discovery of the X-ray; and three years later, Pierre and Marie Curie isolated the highly radioactive element, radium. These and subsequent advances have provided numerous valuable tools, not only for the treatment of cancer but also for cancer diagnosis and fundamental research on the nature of malignant disease.

Beginning of Research on Viruses and Cancer.-Although some investigators had previously suggested that cancer may be caused by viruses, this idea remained without experimental support until Peyton Rous, of New York, showed in 1911 that a tumor occurring in domestic fowl was caused by a virus. This work lay in relative disregard until only a few years ago when interest in virus studies was revived. Today, virus research is one of the most important areas in the broad study of cancer in animals and man.

Treatment of Cancer with Drugs.-Although efforts to treat cancer with drugs were reported as long ago as 1865, these activities were of relatively little value when compared with the present scope of cancer chemotherapy. The modern era in chemotherapy began in 1941, when Huggins in the United States demonstrated that certain forms of cancer responded favorably to treatment with hormones. Then, during World War II, several American investigators, including Goodman, Gilman, and Dougherty, and Jacobson, found nitrogen mustard, a chemical related to mustard gas, effective in the treatment of certain cancers of the blood-forming organs, particularly Hodgkin's disease. These observations were a great stimulus to further research in cancer chemotherapy. In 1948 Farber in the United States found that chemicals that interfere with the ability of cells to utilize folic acid (a vitamin) could produce complete remissions in acute leukemia in children. This research literally put the theoretical approach to cancer chemotherapy on a practical basis, because it indicated that drugs with the special ability to attack cancer cells could be designed and produced in the laboratory. Today, chemotherapy research is probably the largest single facet in the total scientific effort to control

cancer.

Exfoliative Cytology: A New Method for Detecting Cancer.-Two American scientists, Papanicolaou and Traut, reported in 1943 that cancer of the uterine cervix (neck of the womb) could be detected by microscopic examination of fluids obtained from the female genital tract. This technique for cancer detection has been extensively applied and evaluated, and has proved extremely valuable in detecting cases of uterine cervical cancer at a stage when treatment by surgery or radiation is most likely to be curative. Many other scientists are attempting to perfect methods of applying the cytologic test to the detection of cancer of several other internal body sites.