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STATEMENT OF DR. ANTHONY S. FAUCI

Over the past four decades, the research mission of the National Institute

of Allergy and Infectious Diseases (NIAID) has evolved to encompass illnesses

ranging from allergies to AIDS, from the common cold to exotic diseases that

devastate populations throughout the world.

These diverse areas of research

are all solidly grounded in the foundation of our Institute, which is basic

research on microbes that infect people and on the immune system that protects

us against these invaders.

This common theme underlies all of our efforts.

Today, even as biomedical researchers break new ground in immunology,

usher in the era of gene therapy, and design drugs that are highly specific

and effective against a wide range of infectious agents, such achievements

create a new challenge. The public's expectations of what biomedical research

can do to alleviate suffering and death caused by human diseases far surpasses

our available resources.

How then can NIAID best employ its sophisticated technologies to fulfill

its mission of improving public health? The most effective way to narrow the

growing gap between expectations and available resources is to prevent

diseases before they occur.

In the area of infectious diseases, this is best

achieved through vaccines.

Our foundation of basic research and our accomplishments in vaccine

development make NIAID uniquely positioned to lead the renaissance in

vaccinology that is being realized in the decade of the 1990s. Historically.

vaccines have dramatically decreased or even completely eliminated infectious

diseases that have taken heavy tolls on past civilizations.

A classic example

is the complete eradication of the scourge of smallpox from the world.

Nonetheless, we have realized only a fraction of the full potential of

vaccines to prevent a wide array of infections that cause considerable

morbidity and mortality throughout the world.

Over the past several years.

natural products and synthetic peptides of organisms and, most recently.

recombinant DNA products have largely replaced whole killed or attenuated

organisms that have traditionally been used to make vaccines.

These newer

approaches have resulted in more specific and potentially less toxic vaccines.

Something more theoretical, but with considerable potential, is the

concept of Intracellular immunization, which employs a form of gene therapy to "immunize" cells against viral infection.

It involves inserting into an

individual's blood cells a gene encoding for a protein that inhibits the

growth of the target virus.

This past year, several NIAID-supported

researchers identified mutant genes of the AIDS virus that are promising

candidates for such a strategy.

Vaccines benefit people of all ages, but their impact on the health of

children is particularly important. Many of you may be aware of a new concept

known as the "Children's Vaccine Initiative.". First proposed by the executive

director of the United Nations Children's Emergency Fund, its goal is lofty:

immunize children worldwide with an oral vaccine that provides lifelong

immunity to the major infectious diseases of childhood.

NIAID is committed to

focusing our basic research activities on surmounting the technical obstacles

inherent in creating such a vaccine.

In fact, I am pleased to be able to tell you about an important advance in

the technology for producing childhood vaccines.

In 1990, the FDA licensed

two new vaccines to protect infants against Haemophilus influenzae- type B

(Hib), the leading cause of bacterial meningitis in young children.

Each

year, more than 700 children die of Hib meningitis, and several thousand

suffer long-term neurologic consequences of the disease, including mental

retardation and hearing loss.

The new vaccines now make it possible to

prevent Hib disease in children at highest risk for developing severe disease,

those between 2 and 15 months of age.

The Hib vaccines use a new technology with far-reaching implications for

protecting young infants against other serious bacterial infections.

Because

of the immaturity of their immune systems, very young children do not respond

to vaccines made from the outer polysaccharide coats of some bacteria.

NIAID.,

supported extramural investigators and other scientists at the National

Institute of Child Health and Human Development overcame this problem by

pairing the Hib polysaccharide with a pro

ein that children can respond to at

birth.

Use of the Hib conjugate vaccines will save an estimated $359 million

for every annual cohort of children that is vaccinated. This compares with the $17.4 million NIAID spent on research leading to the development of these

vaccines.

We are continuing our search for an improved pertussis (whooping cough)

vaccine, focusing on highly purified acellular vaccines containing only part

of the disease causing bacterium.

An NIAID-sponsored multicenter clinical

trial involving more than 2,000 children is now underway to compare

simultaneously a number of acellular pertussis vaccines with 2 conventional

whole-cell vaccines.

The data generated from this study will be used to

select vaccine candidates for a larger efficacy trial that will begin before

the end of 1991.

Effective control of other, non-infectious diseases continues to be a goal

of NIAID's basic and clinical research endeavors.

Asthma is one of these

diseases and, as I mentioned last year, it is affecting a disproportionate

number of inner-city minority children.

Reports published this past fall

confirmed that despite advances in treatment, the numbers of children who are

suffering and dying from asthma are climbing in the United Stases.

NIAID

recently announced eight awards to establish a network of centers to study

asthma in inner-city children.

The goal of the program is to identify the

factors contributing to this problem and to develop interventions to help

reverse this trend.

We are finding increasing evidence that viruses may directly or indirectly

contribute to the pathogenesis of a broad range of diseases whose etiologies

are unknown.

Last year, a newly discovered human retrovirus was linked to

Sjogren's syndrome, an uncommon autoimmune disease characterized by dryness of

the mouth and eyes.

Recent preliminary evidence from studies of heart

transplants indicates that a virus may accelerate the development of

atherosclerosis.

It appears likely that in the future viruses will be shown

to play a role in at least some connective tissue disorders and degenerative

neurological diseases, as well as cancers.

Fundamental studies in immunology have led to major advances in organ

In the decade of 1990s, organ and bone marrow

transplantation.

transplantation have entered the ma Instream of clinical practice.

Last year 1

told you that NIAID grantees had developed a new hybrid molecule linking

diphtheria toxin to interleukin 2, one of several powerful chemicals known as

cytokines that are produced by the immune system.

This molecule binds to

cells that cause transplant rejection and the toxin kills the cells.

In other

studies, a monoclonal antibody was used to eliminate the cells responsible for

transplant rejection.

A recent clinical trial compared the efficacy of the

new monoclonal in combination with cyclosporine A (standard immunosuppressive

treatment for transplant patients) versus cyclosporine A alone in preventing

early kidney graft rejection episodes.

There was a statistically significant

reduction in early kidney graft rejection episodes in the group receiving the

combination therapy.

History has taught us that new and re-emerging microbes are a constant

threat to the survival of our species.

AIDS offers the most striking example

in recent times of the potentially catastrophic impact of a new infectious

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people are infected, and as of January 1 there have been 160,000 cumulative

cases of AIDS and 100,000 deaths.

AIDS is now the second leading cause of

death for young men ages 25 to 44 in the United States, surpassing heart

disease, cancer, and suicide.

The pattern of AIDS in the United States, however, is changing

dramatically. Increasingly, AIDS is becoming a disease of heterosexuals,

infants and children, women, and minorities.

By the end of 1988, AIDS had

become the fifth leading cause of death in the United States among Black women

ages 25 to 44; by the end of this year, it is expected to be among the five

leading causes of death among all women of reproductive age.

We have taken several steps to identify research needs associated with HIV

infection in women, including establishment of a women's health committee

within the NIAID AIDS Clinical Trials Group, to ensure that the issues

involving HIV-infected women are fully integrated into the NIAID research

agenda.

In December 1990, NIAID coordinated the first national Public Health

Service-sponsored conference on women and HIV infection.

The conference

highlighted how the complex roles of women in the family and society compound

not only their own suffering but also their ability to participate in clinical

research studies.

NIAID has also focused on improving participation of minority constituents

and health professionals in our research programs. To help recruit minorities into clinical trials, we have provided supplemental grants to AIDS Clinical

Trials Units.

In addition, we have recently awarded funds to three

institutions that primarily serve minority populations to help them build the

infrastructure necessary to conduct clinical trials.

This past year has yielded benefits from prior investments in basic and

clinical research in AIDS.

One of the major advances in prolonging the lives

of people infected with HIV has been the use of zidovudine (AZT) and

prophylaxis for Pneumocystis carinii pneumonia (PCP).

Preliminary evidence

indicates that in people with low. 14 cell counts, appropriate therapy doubles

their expected survival time after diagnosis from 12 to 24 months.

AZT, however, is an imperfect drug, and hence we are actively searching

for new drugs to treat HIV infection.

Preliminary studies suggest that the

combination of AZT and dideoxycytidine (ddC), given in alternating doses, has

the same benefit but is less toxic than continuous therapy with AZT.

Another

promising drug, dideoxyinosine (ddl), is being studied in Phase II clinical

trials in parallel with expanded distribution to patients not eligible to

enroll in the controlled trials.

Several studies of interferon alpha, either

alone or in combination with AZT, have been conducted in persons with early

HIV infection.

These studies have shown that interferon alpha appears to both

slow virus production and reduce the risk of developing AIDS-related

opportunistic infections when administered to asymptomatic HIV-infected

persons.

We have also made major strides in treating AIDS-related opportunistic

infections.

As a result of a large multicenter clinical trial, the drug

fluconazole has replaced an effective but more toxic drug as maintenance

therapy to prevent recurrences of cryptococcal meningitis, a life-threatening

infection of the brain and nervous system.

Studies conducted by NIAID and the

National Eye Institute also showed foscarnet to be effective in delaying

progression of cytomegalovirus retinitis, a sight-threatening eye infection

affecting many people with AIDS.

Ther

have been encouraging results from AIDS vaccine research studies

this past year.

Studies in monkeys using whole killed simian immunodeficiency

virus (a monkey AIDS virus) vaccination followed by live virus challenge show

Other developments included the entry of

promising indications of protection.

several new AIDS vaccines into Phase I clinical trials.

We are now confident

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