promise in the treatment of anemia and rheumatic heart disease. Many millions of people in the United States are suffering from illnesses which may be alleviated by the use of cortisone.

In June 1949 the President directed the United States Public Health Service and the United States Department of Agriculture to undertake whatever steps were possible to promote the production of cortisone and investigate its potentialities. The Bureau of Plant Industry, Soils, and Agricultural Engineering for many years has been responsible for the introduction of foreign plant materials. With $18,000 advanced to it in fiscal year 1950 by the United States Public Health Service, the Bureau of Plant Industry is now engaged in the procurement of strophanthus, an African plant reported to yield a chemical precursor for cortisone. Dioscorea (yam) has been reported as another potential source, and studies indicate other plants in widely separated groups of the plant kingdom may be even more promising. It is now generally recognized by responsible Federal agencies that a coordinated effort on a more intensified scale will be necessary to make any significant advance within the near future.

Cortisone is a complex organic compound, a steroid hormone, belonging to a class of substances which includes bile acids, male and female sex hormones, vitamin D, and digitalis. It is normally produced by the cortex of the adrenal glands. Its use for arthritis does not give a permanent cure, its action resembling that of insulin in diabetes. Relapses almost always occur 1 to 2 weeks after administration of cortisone is stopped. The drug is currently given in daily doses of one two-hundred-and-eightieth of an ounce. However, it is now so rare and costly that a single treatment at present rates may cost $100.

There is little prospect that cortisone can be produced cheaply or in quantity from its present sources. It occurs naturally only in the adrenal glands. One thousand pounds of beef adrenals contain only one fifty-sixth of an ounce of cortisone. The compound can be synthesized from bile acids, but again the process gives low yields and is very costly. Some 200 pounds of ox bile yield only 14 pounds of bile acid. After 30 to 40 chemical processes, less than 1 percent of the bile acid is converted into cortisone. Even though cattle were slaughtered solely to obtain this drug, there would not be enough cattle in the world to supply the present and potential demand for this valuable product.

The antiarthritic properties of cortisone depend largely on the unique and specific location of the oxygen atoms in the cortisone molecule. The synthetic chemist at present finds it very difficult to place these oxygen atoms exactly where they are needed. It is necessary, therefore, to find naturally occurring chemicals (precursors) having not only the same general structure as cortisone but specifically having oxygen atoms in the same positions as the parent substance. For these cortisone precursors chemists have turned to the plant kingdom. A group of compounds called sapogenins, obtainable from plants, offer possibilities as precursors of cortisone. There are several thousand species of plants, cultivated and wild, domestic and foreign, which have been reported to contain sapogenins. Those plants which contain the best cortisone precursors found to date are an African vine, and a Mexican yam. However, it is possible that better sources for the production of cortisone may be found in the many plant species which have not yet been investigated.

The cortisone problem is undoubtedly a difficult one but a timely solution will best be achieved by research teamwork in which Government scientists can and should play an important role. Since agricultural materials are the only sources for the quantity production of this compound, its production in adequate quantities is of vital concern to specialists in the United States Department of Agriculture. Funds for this work are not now available within the Department.

The solution to these problems will provide American people with a cheaper and more abundant supply of cortisone, may provide the American farmer with a new and valuable crop, and agriculture will have made an outstanding contribution to American welfare.

Plan of work.-Botanists would collect and identify plants belonging to species presumed to contain sapogenins that can be converted to cortisone. Such plants would then be investigated by chemists to determine whether cortisone precursors are present. When the best plant sources are known, geneticists would breed strains with high sapogenin contents and agronomists would determine optimum growing conditions so that quantity production of the crop could be achieved. Chemists would then investigate and develop methods for large scale isolation of the cortisone precursors present in these plants and the conversion of the precursors to cortisone. Plant material and chemical products valuable for

drug or other purposes may be developed as a related part of the investigations for the economical production of cortisone. The work would be done by the Bureau of Plant Industry, Soils, and Agricultural Engineering and Bureau of Agricultural and Industrial Chemistry in accordance with the following plan: The Bureau of Plant Industry, Soils, and Agricultural Engineering would conduct three lines of investigations: (1) A bibliographic survey to select plant groups of significance to this program, (2) foreign and domestic explorations for plant material, and (3) propagation and testing of introduced plants to determine their potentialities as sources of the drug in commercial quantities.

The botanical bibliographical survey would be made in conjunction with the cooperating chemists of the Bureau of Agricultural and Industrial Chemistry to cull from the published literature plant groups potentially important as sources of cortisone so as to guide the efforts of those engaged in plant explorations.

Exploration for seeds and cuttings of promising plant sources of the drug would be continued and intensified for species of Strophanthus and Dioscorea (yam), the two recognized sources of the drug, and the other plant groups which botanical and chemical studies may uncover. These explorations will be con ducted first in Africa, Mexico, and Central America, and later in southern Asia. Material of both Strophanthus and Dioscorea which have been collected in 1950 will be propagated in greenhouses at Glenn Dale, Md., and grown and tested under appropriate climatic conditions at Coconut Grove, Fla., and Mayaguez, P. R. As soon as chemical investigations by the Bureau of Agricultural and Industrial Chemistry indicate good plant sources for cortisone, a program of rapid propagation, breeding, and field testing will be initiated to evaluate the introductions as agricultural crops either in the United States, its territories and possessions, or abroad.

Chemists of the Bureau of Agricultural and Industrial Chemistry would investigate the plants collected by the Bureau of Plant Industry to determine whether cortisone precursors are present. This would be accomplished by investigations upon the fresh plant material and upon material dried under conditions known to prevent destruction of any precursors present. The plant material would be extracted to obtain a crude sapogenin fraction which would then be further fractionated to obtain concentrates of cortisone precursors. These purified fractions would then be examined chemically to determine whether they can be converted to cortisone in reasonable yields. When the best plant sources are known as a result of the joint efforts of Bureau of Plant Industry, Soils, and Agricultural Engineering and Bureau of Agricultural and Industrial Chemistry and such plants are being grown in quantity, chemists and chemical engineers of the Bureau of Agricultural and Industrial Chemistry would then conduct investigations to develop large scale processing procedures for the isolation of cortisone precursors based on the fundamental studies conducted in the laboratory.

The work would be coordinated with the laboratory and clinical work in the cortisone program of the United States Public Health Service. The Public Health Service is looking to the Department of Agriculture for discovering plant materials valuable as sources of cortisone and for the initial chemical evaluation of such materials and for the development of sufficient crop production to meet the requirements for the production of the drug.

Mr. WHITTEN. It is with great pleasure that this committee notices that you gentlemen are able, willing, and ready to do this work with the personnel and the funds you already have. Now, would you like to make some comments?

Dr. CULLINAN. I would like to have Dr. Hilbert make the opening statement on this.

Dr. HILBERT. Mr. Chairman, would you care for me to describe the importance of the problem involved in the project?

Mr. WHITTEN. We will be glad to hear from you. We have put this material in the record in an effort to save time, so you might limit yourself to why it is necessary to have additional funds.

I directed attention earlier to the fact that every time you have. some new work in the Department, you never seem to have the personnel or the funds to do it, and it always takes new money and new

people. So, you might direct yourself to the necessity for the extra money to do this work, which we realize must be done.

I directed attention to this before and now I would like to know what efforts were made within the Bureau to determine whether you could not do this work without a special request for additional funds. Dr. HILBERT. Mr. Chairman, under our present appropriation structure provision is made to undertake important research on utilization of agricultural commodities. There is no provision for studies on cortisone.

Mr. WHITTEN. Well, the original legislation setting up the Department of Agriculture and subsequent legislation setting up the Bureau of Plant Industry, plus the Secretary's statement of jurisdiction, should give you ample authority not only to do research with cortisone, but thousands and thousands of other things as well.

I doubt, Doctor, whether you mean to say you have no authority to do this. I think you do have ample authority, or else the mere provision of funds would not enable you to do anything.

I do not question the need for this new work. It is certainly highly promising and the whole country is looking for it. I am directing my question now to the effort made in your bureau to give attention to this thing with your present personnel and funds.

Dr. HILBERT. Well, sir, if we were to undertake these investigations under our present funds, we would have to curtail the amount of money allotted to some other commodities.

Mr. WHITTEN. How much money do you have within your Bureau for this kind of work?

Mr. DONOVAN. This particular item is carried under the financial project "Sugars and special plant utilization investigations," for which in fiscal year 1951 there was originally provided, prior to this supplemental estimate for cortisone work, $544,758. That is for the general project.

Mr. WHITTEN. And even though you have these scientists in the Bureau, you would not think of assigning anyone from any other section except the one that has to do with the subject matter you just read to the committee.

Now, gentlemen, I wish to point out as I have many times here that, according to the release of the Budget Office, the budget for next year increases the number of employees in the Department of Agriculture over 2,600. There has been a continual and gradual process of building up the Department.

I have told you many times that every time a new problem comes up, it takes new personnel and additional money. You do not seem to be able, within the limits of present personnel and funds, to be selective to the point of slowing up some projects and picking up on others that seem highly promising, as does this cortisone. That does not hold merely with your Bureau but with the whole Department. Now, I do not mean to embarrass you gentlemen, but I think that all of us should be interested in the fiscal situation of the Government. Now, has there been any effort to see whether you could carry on this work with your present personnel and carry it on right? Dr. CULLINAN. May I speak for our Bureau, Mr. Chairman? Mr. WHITTEN. Yes.

PLANT INTRODUCTIONS

Dr. CULLINAN. We have the responsibility of exploring for plants which we bring in for evaluating and testing as the most promising for various uses. We did not have funds available this year when the letter came down from the President to the Secretary of Agriculture, explaning the importance of this work and asking if the Department of Agriculture and the Public Health Service could not consider ways of immediately activating this program.

The Public Health Service does not engage in exploration for plant materials. That has been the responsibility of our Bureau, and we did not have funds at that time to immediately send out botanists on an exploring trip to West Africa, where the Strophanthus plant reported to contain the drug cortisone is abundant.

EXPLORATION FOR STROPHANTHUS

So, the Public Health Service provided $18,000 to take care of the travel costs and salary of an explorer to go into west Africa and collect this plant. We were asked to locate sources of the plant and bring back seed and parts and then turn them over to the Public Health Service for study to determine the presence of this promising drug in the plant.

Now, it so happens that as part of our work we had previously brought in one species of this plant in 1927 and we had it growing in our field station at Coconut Grove, Fla. That was in line with our work of introduction of plants to see if they have any commercial promise or value of being agricultural crops or drug plants. At that time it was not known that this plant had particular promise as a source of cortisone and so we had not gone ahead and made agronomic studies of it, and evaluated it like we have many others.

It has been pointed out that this very valuable drug is present elsewhere and also could be collected from cattle but the supply is so small that it would not be sufficient to take care of the 7,000,000 cases of arthritis in this country. So the Public Health Service asked us if we could do something in order to bring in quantities of Strophanthus seed for immediate use. We had no money for exploration or study but we were interested and anxious to cooperate. The Public Health Service provided the funds to do this work.

Now, as the result of that exploration we have brought in not only parts of the plant but a quantity of seed and we are doing what we can to propagate the seed at our Glenn Dale, Md., station. However, if this program is to go ahead and advance, as we feel it should, we do not have the funds for testing that material throughout the southern United States to find out where it is adapted and where it will produce seed.

NEED FOR WORK ON OTHER PLANTS

This budget request that we are making envisages an expansion of this program so as not only to test the value of this particular plant which at the present time has not been demonstrated as the best source of cortisone. but also to test the yam and other plants. I do not mean the sweet potato but the true yam. We have evidence that it also

contains precursors of this drug, and it may be that some other of our cultivated plants in this country contain this drug.

Now, that is as far as we can go in our work. We do the agronomic work. Somebody else has to take the work beyond that stage and make the necessary extractions and run chemical analyses to determine whether the plants contain the drug. In addition to that, the Public Health agency has to run the clinical tests.

Our part of the program is, with the aid of the botanists who know the plants and their characteristics, and the regions in which they grow, to bring them in and learn how to produce them in quantity and make them available to the chemists and others who will use them.

Mr. WHITTEN. Doctor, you have made a good statement. I know you will not misunderstand the attitude of the committee. We do not want to take it on ourselves to be responsible for blocking any program in a field as vital as this is to so many of our American people. But we wish to point out that every time some new subject comes up it always ends like this.

Dr. CULLINAN. Well, sir, we are entirely in sympathy with that viewpoint, Mr. Chairman, and we have taken these facts into consideration before requesting additional funds.

RESEARCH ON GLADIOLAS

Mr. WHITTEN. There is another point. For over 2 or 3 years I have advertised your Bureau among the departments. I pointed out this gladiolus situation where for several years the gladiolus people were all upset because the Congress did not appropriate special money for that flower. But we had a lot of money appropriated to your Bureau for diseases of flowers, and last year the committee felt that your personnel should give attention to diseases of all flowers, including the gladiolus. And in our report, in lieu of earmarking an amount for research on the gladiolus and other flowers, the conferees directed the Department to give proper study to gladiolus, within the amount granted.

Now, the gladiolus people contend that you did not give them their rightful share of attention, even after this directive of the committee. Now, what is the true picture on that?

Dr. CULLINAN. Well, the true picture, Mr. Chairman, is that we have attempted to give the gladiolus people all the assistance that we could within the framework of the funds we had available. The situation is this.

When this problem was first called to our attention in 1948, that is, the increase of diseases of gladiolus in Florida, we transferred $5,000 from other floricultural studies to the gladiolus problem, and increased the amount we were spending on that from $13,000 to $18,300. Mr. WHITTEN. That is, on gladiolus?

Dr. CULLINAN. That is on gladiolus, and last year when the committee directed us to give attention to gladiolus, although we had to absorb $8,650 in our ornamental crops unit because of the pay act, we increased the amount of gladiolus money by $6,700 and we now have allotted from our appropriated funds $25,000 on that crop. This is more than we are spending on a large number of other important