NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN

DISEASES

STATEMENT OF DR. LAWRENCE E. SHULMAN, DIRECTOR

SUMMARY STATEMENT

Senator HARKIN. The subcommittee will resume its sitting. Our last panel is here and we will do the same thing, we will just go down the line and have questions after you all testify. Again, as before, all of your statements will be made a part of the record in their entirety, and if you would summarize them I would appreciate it.

First is Dr. Shulman, from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Your Institute now is 4 years old?

Dr. SHULMAN. Yes, sir.

Senator HARKIN. And up and running. We look forward to hearing your statement. Your request for next year is $176.08 million, that is a 4.23-percent increase.

Dr. Shulman, again, welcome and please proceed.

Dr. SHULMAN. Mr. Chairman, once again, it is a great privilege to appear before you on behalf of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. I repeat the name again only to emphasize that we have a very large research mandate.

Within those three names are five different fields of medicine, and each of them has a broad and deep research agenda. For example, there are over 100 different types of arthritis, as you know, and the numbers of skin diseases are even larger than that.

I will briefly share with you some of the highlights this year. We have had a very good year in terms of research accomplishments. Let us start with Lyme disease. It is still increasing, as you know, and is the most frequent vector-borne disease in the United States. We discussed last year the problem of diagnosis. It is underdiagnosed early, overdiagnosed late.

We needed some new tests and we have now developed such new tests. One of the researchers we support has developed a test for detecting Lyme disease in the urine. Using the polymerase chain reaction, as Dr. Fauci mentioned this morning, intramural scientists at the Allergy Institute have developed an excellent new test to pick up very small numbers of bacteria in the tissues, in the joints, for example. Also we are able to grow the organism from the blood of patients with this disease. Therefore, we have made some progress in this arena.

We do not know what the bug does in the body. Here, we have an example of even when knowing what the causative agent is, we do not know how it produces the disease, especially its late manifestations.

For that reason, we and the Allergy Institute issued a request for applications for research on the causes of Lyme disease. We received 45 research applications from that announcement, and as a result we will be able to support some excellent research as to how this disease comes about.

Now let us now turn briefly to arthritis research. We have had some encouraging developments. As you know, sharing your interest, we have been working hard on the whole question of finding infectious causes of arthritis.

We issued a program announcement for more research, and we have done well. You asked us to support $5 million this year on infectious and other causes of rheumatic diseases. In research on infection alone, we will be expending more than $5 million in 1990. In 1989 we expended $4.9 million, supporting 31 grants, three on mycoplasma which is an area of special interest to some.

We made progress on the treatment side. Methotrexate has proven to be a very effective treatment for rheumatoid arthritis and has just this year been approved by the FDA. We have other effective agents for other types of arthritis as well.

We have much going on in osteoporosis. As you know, our Institute is the lead agency for osteoporosis research. We have new findings on mechanisms of bone loss and we have made progress on how to measure bone density, new techniques have been developed. We have other studies on fluoride, which will be published shortly, of a long-term study indicating that there is a difference between what you measure in terms of bone mass and the quality of the bone. It indicates that we need even better measurements than the ones we have today. Moreover, we have developed new data with respect to both preventive strategies and treatment strategies for osteoporosis.

I could go on, but will not do so. We have new developments in research on lupus and on osteoarthritis, and on the severe blistering diseases of epidermolysis bullosa and pemphigus that are both serious skin diseases.

I would like to close with just two points. The first, and the major one, is that we have appreciated your interest in our intramural research program. We started off with a rather modest intramural program, and you advised us, and in fact ordered us, to spend a part of the increase you gave us this past year in developing further the intramural research program.

We have done that. The NIH has given us some additional space, and we are very grateful for that, to develop the intramural program. We have recruited a new laboratory for skin biology with Dr. Peter Steinert as its director.

We have had very gratifying developments with the orthopedic research program. Also we plan to initiate a laboratory of structural biology, which will be a great resource for all at the NIH.

We expect to have additional space coming down the pike, as promised, and we have plans for further development of the intramural program.

PREPARED STATEMENT

Last, we have developed the organization for developing our national plan. I have awaited, as you know, senior staff to come and join with me for that. We were able to recruit Dr. Michael Lockshin, a professor of internal medicine from Cornell, to join our Institute as the head of extramural programs. He and I, along with a deputy director, also to be recruited and appointed, will be leading that effort which will take some 21⁄2 years, and we have to spread our resources over those 21⁄2 years to support and accomplish this special, comprehensive mission.

STATEMENT OF DR. LAWRENCE E. SHULMAN

It is my great privilege to share with you some of the accomplishments, latest research advances, and opportunities for research by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) this past year, and to present some of our plans for the future. The mission of the Institute embraces a wide variety of disorders; most of which are long-term and disabling. These diseases affect millions of Americans, exacting an enormous toll in human suffering and placing an immense economic and social burden on the Nation.

One of the most rapidly growing problems is Lyme disease, which affects many parts of the body and is caused by screw-shaped bacteria that are transmitted by ticks. Some 5,000 new cases were reported last year; and it is increasing. Because its symptoms closely resemble those of other illnesses, early diagnosis of Lyme disease is often difficult. hopeful that a urine test, developed by our researchers, that uses highly specific antibodies will prove to be a better diagnostic instrument than

the blood tests now available.

We are

Another promising lead has emerged from a

US-USSR study, showing the existence of Lyme disease in different regions of the Soviet Union, and apparent differences in the strains of the This could explain regional

causative bacterium in the different regions.

differences in the expression of Lyme disease.

To encourage more research on Lyme disease, the Institute has issued, jointly with the National Institute of Allergy and Infectious Diseases, a request for applications pertaining to its pathogenesis. The NIAMS has also issued a program announcement focusing on clinical and epidemiological research on Lyme disease. The responses to these two initiatives have been highly encouraging.

Rheumatoid arthritis is of major concern to our Institute and to the 2.1 million adults in the United States who suffer from it. Good news with

regard to the treatment of this potentially crippling disease was

establishing the efficacy of methotrexate.

Definitive therapeutic trials

have reconfirmed its safety, and the Food and Drug Administration has recently approved its use for treating arthritis.

This year, the NIAMS is initiating a multicentered clinical trial of minocycline (a form of tetracycline) for the treatment of rheumatoid arthritis. It is based on the recent demonstration that minocycline inhibits the activity of collagenase--an enzyme that breaks down cartilage and bone in the joint. If the drug proves beneficial, investigators might then develop and evaluate a new form of tetracycline that retains the collagenase-inhibiting properties of minocycline, but not its antibiotic

properties.

The Institute is pleased by the response that its program

announcement, requesting research proposals on infectious causes of rheumatoid arthritis, has evoked. This year, a new approach has emerged for the study of this important area. For the first time, researchers have succeeded in genetically manipulating mice to carry a specific genetic

trait that is closely associated with spinal arthritis in man. The ability of infectious agents to induce arthritis in these mice is being evaluated. Numerous Americans, largely young women, suffer from systemic lupus erythematosus (lupus), an inflammatory, immune-mediated disease that causes distinctive rashes, arthritis, and life-threatening kidney damage. Lupus is found much more frequently in women than in men (9 to 1) and affects more blacks than whites (3 to 1). Recent research indicates that different autoantibodies, antibodies that react against the body's own tissues, are closely related to specific clinical features of lupus. From sophisticated immunogenetic investigations, we are learning that immunologic abnormalities are frequently found in female relatives of lupus patients, thus providing valuable information about how the disease is genetically Important questions remain regarding the epidemiology of lupus and the undiscovered factors that trigger the immunological defects. The Institute is also encouraging enhanced research on other major rheumatic diseases: arthritis of children in its many forms; Sjogren's syndrome;

linked.