irradiation, and those are still the two main tools we have in attacking any problem of cancer in the human body. This is work which was begun by the great work of the Cancer Institute and a number of institutions of the country, this concept of the use of a chemical compound which may be taken by mouth, which might affect not only acute leukemia but cancer of the breast, the prostrate, the intestines, or the brain. When I say chemical in this connection I might use the word "hormone." Now, the results of this work came from laboratories, from cooperation of chemistry and bacteriology in laboratories and colleges and medical schools, and the pharmaceutical industry far removed from the patient, and I want to emphasize again that without the support of these basic workers such a necessary step could not take place. Dr. Rhoads has mentioned the splendid cooperation from the pharmaceutical industry which has rich resources in manpower, talent, and equipment and money which is contributing to the benefit of those who are interested in cancer research. In the case of acute leukemia, beginning in 1947, there was the first marked change in the treatment involving administration of chemical compounds related to a vitamin, but different in a very important biological way from the basic vitamin because of its effect in prolonging the life of children with acute leukemia. Since that time in several laboratories and clinics there have been advances made with the use of ACTH and cortisone and with other chemical compounds totally unrelated to the first group, and with all of these techniques today we are able to control acute leukemia in children more successfully than ever before. The point I wanted to make was that despite these great advances this form of cancer is still incurable. We are able to reduce the pain for long periods of time, and we are able to increase the period of survival of these patients, and we have reached into a condition which used to cause death after a few weeks or months, and we are able to extend survival for a year or 2 years. The longest survival we have is that of a little boy, and it has been 2 years and 4 months since the onset of his leukemia. However, he is still suffering from acute leukemia which may arise at any time to end his life. We are also interested as a result of the atomic bomb with which leukemia has been produced in those individuals who have the proper substrata for leukemia, and we may expect a great deal more should there be an increased use of that weapon. X-ray men have 8 or 10 times the leukemia of doctors in general, showing that those who are exposed for long periods of time to the action of X-rays may have a condition or stimulus which results in the production of acute leukemia. I am not going to carry on this discussion any farther trying to give other examples. This is similar to the examples Dr. Rottino described in Hodgkin's disease. In the last 8 or 9 years men in a number of places, Dr. Rhoads' group, and people in Chicago, have administered compounds which originally came from the war gas, nitrogen mustard, thus using it in a much more effective way in an attempt to prolong life. That move, as a matter of fact, was the starting point of this whole modern way of treatment of human beings with cancer by chemical agents. I wonder, Dr. Heller, if I may continue for just a moment so that I will not interrupt later on, and comment on one of the points which the chairman was obviously considering this morning. May I return to the question of the number of hospital beds? In the first place, I would like to agree with Dr. Rhoads' estimate of the tremendous cost of hospitalization of all patients affected with cancer in the country. This is in addition to the amount of money which has been given through the National Cancer Institute and other organizations such as the American Cancer Society and the Damon Runyon Fund, for research in stimulating better care and developing new methods of treatment. However, I think in answer to your question, Mr. Chairman, any bed in the country is a cancer bed, just as any doctor in the country is interested in the subject of cancer, not only those who work in the cancer field themselves. I would like to say that when you speak of a hospital bed you must not only put the patient in the bed, but surround him with doctors who are properly trained and a sufficient number of nurses and technicians and all of the other medical workers who are needed to give that patient with cancer the kind of care that is given to the patient in those hospital centers where the best kind of cancer care is given. I will say in direct answer to your question, and I will speak as a doctor interested in the care of patients with cancer, that there are certainly not enough beds in the country, nor are those who have cancer in the position throughout the country to pay for this perfectly tremendous cost of medical care when they have months or even years ahead of suffering from cancer. I would like to record that as one man's experience and one man's opinion. The CHAIRMAN. When you speak of basic research you are speaking of a subject that this committee has already shown great interest in because it is through this committee that the National Science Foundation was formulated, both legislatively and otherwise. So, we are very pleased to hear you speak in the terms which you do about basic research. Mr. Dolliver. Mr. DOLLIVER. You referred to the disease of leukemia as a cancerous condition of the white blood cells. Would you differentiate that from the disease anemia which also is a disease of the white blood cells? Dr. FARBER. The word "anemia" is a general term which refers particularly to a reduction in the number of red cells and more generally to a deficiency of the bone marrow and those portions of the body which manufacture red cells or other cells which we require. In leukemia the bone marrow is destroyed or replaced by the cells of the white source. There is no room for the production of adequate numbers of red cells. So, anemia is one of the more important symptoms of leukemia. Anemia, generally speaking, is much broader. That may be broken down into specific classes. One of these is called pernicious anemia. That one can be kept under control for the lifetime of a patient by the use of liver and liver extracts or other substances. There are many different causes of anemia as there are many different kinds of cancer. Mr. DOLLIVER. Am I correct in thinking that leukemia and anemia are two separate and distinct things? Dr. FARBER. Yes. Mr. DOLLIVER. May I address a question to Dr. Rhoads? Ι The CHAIRMAN. Yes, certainly. I have been impressed with your knowledge of medicine and any questions you ask, I assume, will add to your knowledge. Mr. DOLLIVER. I very quickly admit I need to add to my knowledge, Mr. Chairman. In one comment that you made, Dr. Rhoads, you said that there was some stimulus given to the search for a specific chemical_control of cancer by the experience gained during World War II. I would be glad if you would care to develop that idea and trace the source of that renewed interest. Dr. RHOADS. The stimulus should have followed World War I, but people were too uninterested in cancer to see that obvious control which was under their noses. There was organized during World War II a Medical Division of the Chemical Warfare Service. Its mission was to study the way in which poison war gases exerted their injurious effects so that we could devise means for protecting our troops. I may say we had in mind means of taking specific hills without any casualties, but they were never employed. Mr. DOLLIVER. Am I correct in saying that during World War II no poison gases were used in combat? Dr. RHOADS. That is correct, yes, sir, except by accident. Mr. DOLLIVER. Yes. Dr. RHOADS. On the night of December 3, 1943, Bari Harbor was bombed. We were unloading munitions that night there, and there were some 14 ships at the mole discharging. One of them had aboard a cargo of airplane bombs, and that included 100 tons of M-I bombs, charged with mustard gas. We had stocks of chemically charged munitions on the European front in case gas was used against us. The harbor was a mass of flame, and over a thousand men were in the water because a whole series of ships went up in the explosion. Men were pulled out and sent to 2 hospital stations under the charge of 2 different medical officers. They were covered with oil and suffering from submersion. One medical officer cleaned the oil off before he put the men in warm blankets and gave them the customary treatment. The other officer did not do so. All of the men in the second group died and none of the men in the first group died. I had a very good officer, Colonel Alexander, who was then in the North African theater. We heard about this, and we made post mortem examinations of the men who died, and the tissues were sent back to our laboratory at the Edgewood Arsenal by regular channels also and subjected to pathological examination. It was quickly apparent that the men had died because all of the cells normally forming the white blood cells, that is, the structural units and the bone marrow and the lymph glands, had been destroyed. We should have known this before, but we did not. There had been a suggestion of this right along. That led to consideration of the possibility that since there were forms of cancer arising in blood-forming tissues of lymph glands, as Dr. Farber has explained, and since these war gases destroyed the normal bloodforming cells, they might destroy cancer arising from those bloodforming cells. We had under contract with us Dr. Gilman and others-Dr. Phillips at Yale University-working for the Chemical Warfare Service. They had a patient who had an advanced cancer of the lymph glands of his neck. These are the glands that swell up when you have a sore throat. You can feel them in your neck. This was so extensive it was blocking off his windpipe and threatening strangulation. They could not make a hole in his windpipe because the cancer was too far down. He agreed to have a test dose of one of the mustard gases used. This was administered and his cancer simply melted away, within a matter of hours or a few days. That was the first trial of a mustard derivative in the treatment of cancer in human beings. Mr. DOLLIVER. What was the approximate date of that? Dr. RHOADS. 1943. Mr. DOLLIVER. 1943. Dr. RHOADS. As I recall it. Either late 1942 or 1943. I have forgotten for sure. Then we extended the work to Chicago, where Dr. Jacobson made the first observation of this first same effect, operating in Hodgkin's disease. All this work was done under Army contract with the division. We then put out the chemicals under military security to a number of hospitals which wished to cooperate, still under military security, and had a rather extensive clinical trial. That was against various kinds of cancer by the time the war ended. This was done with the understanding and cooperation of the National Research Council, as Dr. Cannan recalls. We were able to report not long after the war, when security was removed, trial in a very large number of institutions, which gave us sound information completely reproducible on what these chemicals would do and what they would not do, and some information on their mode of action, which has led to the whole program of synthetic preparation of similar chemicals, related chemicals, and a knowledge of the kind of chemicals you might predict would have some of the effects Dr. Farber specified. As he says, I think this was the key. We had all been groping for this, which gave us for the first time at least some little rational basis for a program of seeking for a penicillin for cancer, which we have not found yet; but I hope we will. Mr. DOLLIVER. This series of events which you have now related is the basis for your hope for a penicillin, as you say, for cancer, I take it? Dr. RHOADS. Yes. There is lots more information now, much of it derived from Dr. Farber's studies, suggesting this is not an unreasonable hope. Mr. DOLLIVER. If Dr. Farber has anything to add I would certainly be glad to hear it, because this whole area of discussion, Mr. Chairman, is something quite new to me. I had not realized that this phase of cancer had developed to the point where it apparently has. Dr. RHOADS. Certain very striking psychological hurdles have been surmounted now. A. We know these effects Dr. Farber refers to can be exerted in animals and human beings. B. We have good test objects by which we can assay the ability of newly synthesized chemicals and select for injurious effect upon cancer and normal cells. C. We have a little understanding of how they work and we can institute a program of synthesis on a semirational basis today. I think most important of all, we have very real knowledge that the cancer cells do not differ in certain respects from other cells, and so should be susceptible to selective attack. We can show this in the test tubes, with experimental animals and to a limited extent now in human beings. Mr. DOLLIVER. Would you have any idea how many different chemicals you have tested in this research? Would it run into the hundreds? Dr. RHOADS. Our group has tested 10,400 pure chemicals and 7,000 crude abstracts of natural materials; yeasts, molds, running all the way from grapes and apple parings to mushrooms from Western Germany. There are natural materials such as these mushroom strains, active agents, which will restrain today cancer in experimental animals. Whether they will ever restrain cancer in man I do not know, but everything looks as though we could hope for more effective means for cancer control in man. A note has been handed to me pointing out that the committee is going to visit New York. Of course we would be happy to demonstrate the operation there at any time you can be in New York. Mr. DOLLIVER. Do you have anything to add to that, Dr. Farber? STATEMENT OF DR. SIDNEY FARBER, CHILDREN'S HOSPITAL, BOSTON, MASS. Dr. FARBER. I might say, Mr. Chairman and Mr. Dolliver, that we have at the present time in a number of institutions in the country a large number of patients with advanced cancer, incurable by other methods, who are receiving these chemical compounds which have been proved to be safe for use in man on the basis of animal experimentation. This is one of the great fields of development at the present time. In the field of leukemia, Hodgkin's disease and the lymphomas these chemicals have had their greatest use so far. The hope is that these chemicals which we have today, or similar ones, may be found effective against other forms of cancer in man. I might say a word of appreciation to the congressional Committees on Appropriations which studied some of the questions we are discussing today. They made special provision for the support of research through the National Cancer Institute, and in the last appropriation particularly concerning the use of chemical compounds in the treatment of leukemia and allied diseases. It is hoped that this special support carried out in a very well-regulated cooperative program throughout the country and through the National Cancer Institute will be enlarged in the course of time to take in other forms of widespread cancer. Mr. DOLLIVER. I am reminded that the Federal Government has a large program of remedial hospitalization in the Veterans' Administration. Have they done anything in the field of cancer? |