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NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY

DISEASES

STATEMENT OF DR. PHILLIP GORDEN, DIRECTOR, NATIONAL INSTI.

TUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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BUDGET REQUEST Senator HARKIN. We will call Dr. Gorden from the Diabetes and Digestive Kidney Diseases Institute.

Senator REID. I only have 4 minutes' worth of questions.

Senator HARKIN. Dr. Alexander with Child Health and Human Development; Dr. Hoel, Acting Director for the Institute on Environmental Health Sciences; Dr. Schambra of the Fogarty International Center.

Dr. Gorden, we have your request for $658.5 million, which is about 6.6 percent more than last year. About $34 million, or almost 80 percent, of your increase is focused in the area of research project grants with funding for centers and training again almost flat, as I have been repeating here in every instance. In fact, the portion of your budget not devoted to research grants increases from-well, it's a 4.2-percent increase, and funding for research grants increases about 7.5 percent.

So, again, Dr. Gorden, welcome back to the subcommittee. We would be pleased to hear your statement. Please proceed.

Dr. GORDEN. Thank you, Mr. Chairman.

Last year on the occasion of our 40th anniversary, we reviewed major clinical accomplishments of the National Institute of Diabetes and Digestive and Kidney Diseases, including the treatment of end-stage renal disease with dialysis and transplantation, major accomplishments in the treatment of chronic hepatitis, and in transplantation for end-stage liver disease.

We reported on treatment strategies in diabetes and the discovery of the abnormal gene that causes cystic fibrosis.

In fiscal years 1991 and 1992, we plan a strong basic science program to build on these major achievements. Our scientists have demonstrated, in the laboratory, that the abnormal cystic fibrosis gene can be replaced in tissue culture cells and correct the disease.

The abnormal gene in a rare form of kidney disease has been discovered. This is the first time a specific genetic defect in a kidney disease that can lead to end-stage renal disease has been elucidated.

We continue to make progress in understanding the cause of insulin dependent diabetes and in developing strategies that may be applicable to its prevention. In noninsulin dependent diabetes, which has such a devastating effect on our minority populations, we continue to make progress in understanding the complex genetic causes of this disease. Incidentally, over one-half of individuals with noninsulin dependent diabetes are over 65 years of age.

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Our endocrine program continues to make important contributions to diseases such as osteoporosis and cancers of the thyroid and prostate gland.

Our hematology program has demonstrated the effectiveness of the biotechnology-engineered erythropoietin for the treatment of the anemia of end-stage renal disease and of AIDS.

Hydroxyurea has been shown to be important in the treatment of sickle cell disease.

Our digestive diseases program continues to pursue clues to the causes and cures of inflammatory bowel disease.

PREPARED STATEMENT Our nutrition program has demonstrated the differences in ways individuals burn calories that they eat, a process fundamental to understanding how to prevent and treat obesity.

For this multifaceted program, Mr. Chairman, our budget request for fiscal year 1992 is $658,557,000.

I would be happy to answer any questions that I can. [The statement follows:)

STATEMENT OF DR. PHILLIP GORDEN

I am very pleased to testify about the programs of the National Institute

of Diabetes and Digestive and Kidney Diseases (NIDDK).

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occasion of our 40th anniversary, we reviewed several major, long-term

clinical achievements of the NIDDK.

These included progress in kidney

dialysis, liver and kidney transplantation, and recombinant DNA commercial

production of insulin, human growth hormone, bovine growth hormone, and

erythropoietin. These advances represent dramatic treatments for diabetes and

liver and kidney diseases, as well as major innovations in American industry

and food production.

As we enter the last decade of this century, our mission

continues to be the advancement of science to improve the health of the

American people and to prevent disease.

Our major programs encompass diabetes

and other endocrine and metabolic diseases; digestive and nutritional

disorders; and diseases of the kidney, urinary tract and blood. Underpinning

targeted research on these serious health problems are crosscutting areas of

science such as molecular understanding of the human genome.

One of the most important NIDDK crosscutting areas is genetics, as

exemplified by our cystic fibrosis (CF) research program.

Last year, I

reported a significant achievement in human genetics research:

the discovery

by NIDDK grantees of the gene and defective protein product that cause CF.

Building upon these discoveries, NIDDK grantees have now taken other giant

steps forward in CF research.

Recently, they successfully established long

term cell culture systems, which can be manipulated to understand and

interrelate more fully the structural and functional characteristics of CF. This past year, NIDDK grantees were able to correct cf in experimental cells

in the laboratoryo-a significant milestone in CF research.

Using a virus,

they inserted & normal copy of the CF gene into pancreatic cells taken from CF

patients. Remarkably, the gene-altered cells produced a normal protein

product and attained normal chloride ion transport.

These findings suggest

that CF is an excellent candidate for emerging gene therapy techniques.

As we now move into the fifth decade of NIDDK research, I am pleased to

report yet another landmark in molecular genetics.

NIDDK grantees have

identified the gene and mutations responsible for Alport's syndrome, an

inherited disease of the kidney's filtering system.

This discovery is

particularly significant because it is the first primary disease gene ever

identified for a disease of the kidneys.

For the many inherited diseases within our mission, the NIDDK is in the forefront of research related to gene therapy. Recently, NIDDK grantees

developed methods for targeting gene therapy to specific sites in animals--the

liver, muscle, and arterial wall.

This research is extremely important

because many inborn metabolic diseases will require organ-specific gene

therapy.

In this regard, the Institute is encouraging studies of genetic

expression and recombination; gene targeting; stem cells and growth factors;

and gene transfer techniques.

The NIDDK is also committed to research aimed at preventing chronic

diseases, and at halting or slowing their progression.

For example, we are

supporting a major, multicenter clinical trial to determine whether strict

control of blood glucose levels can prevent or ameliorate the vascular

complications of insulin-dependent diabetes. Another multicenter trial is

assessing whether a dietary regimen, combined with blood pressure control, can

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prevent or slow the progression of chronic renal disease to end-stage renal

disease.

Such efforts offer the hope of reducing the enormous suffering and

costs of chronic diseases, which will escalate as our population ages.

This past year has been a particularly impressive one for research on

diabetes, which affects over 11 million Americans at an estimated annual cost

of $20 billion.

The NIDDK program in diabetes is a comprehensive one, aimed

at understanding the genetic and other causes of both the juvenile and adult

forms of the disease; finding ways to combat the devastating complications;

and alleviating the disproportionate impact diabetes has on our minority

populations, including Blacks, Hispanics, and Native Americans and Hawaiians.

An exciting discovery in research on insulin-dependent diabetes is that a

pancreatic protein previously known to be an early predictor of the disease is

identical to an enzyme normally produced in large quantities in the brain.

This knowledge should facilitate the development of a simple blood test to

identify--years in advance of clinical disease--those children who are

destined for autoimmune destruction of insulin-producing cells. Such

knowledge will be valuable as more effective drugs are developed that might

arrest the disease in its earliest stages.

Research on restoring insulin

production to diabetics also moved forward this year when NIDDK grantees

successfully used the thymus of rats as a new site for transplanting insulin

producing cells.

With this approach, they enhanced both immune tolerance to

grafts at other sites and graft survival.

Progress is also being made in understanding non-insulin-dependent

diabetes.

Glucose transport mechanisms are emerging as a major new target for

potential treatment of this disease. Studies in animals are defining more

precisely the cascade of molecular events involved in the production and

action of insulin, in order to pinpoint how resistance to insulin occurs.

In

related research, scientists have identified the cell receptor that binds

drugs used to treat non-insulin-dependent diabetes, thus paving the way for

more effective drug development.

A key source of knowledge about the

metabolic abnormalities and complications of non-insulin-dependent diabetes

are NIDDK studies of the Pima Indians, who have the world's highest prevalence

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fruits of success with the identification of a linkage of a genetic locus in a

rare form of non-insulin-dependent diabetes.

The genetic puzzle of diabetes

remains a complex challenge, however.

To help meet this challenge, I am

pleased to tell you that the Institute will begin a new Diabetes

Interdisciplinary Research Program in 1992 in an innovative partnership with the Juvenile Diabetes Foundation, International. This follows a productive

partnership previously established with the Cystic Fibrosis Foundation.

For kidney and urologic diseases research, I am pleased to report several

exciting scientific events.

With NIDDK grant support, kidney researchers have

made inroads in understanding polycystic kidney disease (PKD), in which cyst

formation can impair and destroy kidney function. Recently, NIDDK grantees

discovered that the combined action of two known growth-promoting chemicals

can initiate cyst formation. This finding has already resulted in the testing

of candidate drugs in mice with PKD, thus opening new therapeutic windows.

In seeking to combat end-stage renal disease (ESRD), the NIDDK is

supporting studies to understand the strikingly high incidence of the kidney

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