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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.
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.
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.
of the immaturity of their immune systems, very young children do not respond
to vaccines made from the outer polysaccharide coats of some bacteria.
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
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
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
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.
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
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
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 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.
studies, a monoclonal antibody was used to eliminate the cells responsible for
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
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
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
In December 1990, NIAID coordinated the first national Public Health
Service-sponsored conference on women and HIV infection.
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
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
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).
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.
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
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
We have also made major strides in treating AIDS-related opportunistic
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.
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