The ASM recommends a 6 percent increase in the budget for NIH in FY 2006 and believes this increase would improve the pace of scientific investigation and the translation of science into new and better approaches to prevent, diagnose and treat diseases. A funding increase of this magnitude would allow NIH to take fuller advantage of innovative tools and technologies and the many extraordinary research achievements that have been made during the recent past. It would help to respond to urgent disease threats and realize more of the important medical treatment and public health goals that loom on the near horizon.
The ASM considers a 6 percent increase justified for NIH if it is to continue current programs and deal with new and pressing needs, including the threat from pandemic influenza, other emerging infectious diseases such as the recent and unexpected outbreak of SARS, the AIDS pandemic, a myriad of infectious and chronic diseases that continue to take a human toll worldwide and biodefense initiatives.
Since FY 2003, the NIH budget has flattened, and at less than 1 percent, the proposed FY 2006 budget increase will result in difficult funding decisions for research programs. Because the budget request for NIH falls below the current biomedical rate of inflation, which is about 3.5 percent, biomedical research will face a slowdown in the pace of scientific progress. This static state in funding comes at a rare time with unprecedented opportunities for major advances in human health and also at the very time that our nation’s competitors are significantly increasing their investments in research. Their investments are based on the demonstrated positive impact of biotechnology and biomedical research on economic development. The European Union has set a goal of becoming the most competitive knowledge based economy in the world by 2010. Without increased investment in federally funded research in the U.S., we stand to diminish the growth of US technology.
Basic Research and Training
The ASM emphasizes the importance of providing increased support for basic research and the training and participation of young investigators in biomedical fields. Basic research and human ingenuity provide the underpinning of new knowledge that is necessary for successful medical breakthroughs. Basic research drives scientific creativity and productivity, making increased funding for investigator initiated research project grants a particularly critical issue when making funding decisions. Under the proposed FY 2006 budget for NIH, the total number of research project grants (RPGs) supported falls below that of FY 2005 by over 400 and no inflationary increases are provided for direct, recurring costs in noncompeting RPGs. The ASM recommends increased funding for NIH to ensure a continuum of high quality research project grants and scientist training programs to keep biomedical research in the future as vigorous as it is today.
Specifically, ASM draws attention to the fact that scientific knowledge of microbes and their role in life and in the environment is key to new discoveries that will benefit human health. For example, the study of microbes resulted in the discovery that DNA is the genetic material of life and was responsible for the molecular revolution that has transformed biology. Research into basic life processes of bacteria is a critical underpinning of cellular studies that contribute to progress in the life sciences. Research on bacteria is urgent because more bacteria are becoming resistant to antibiotics, raising the specter of untreatable diseases. NIH should increase support for basic microbiology research and training and review research portfolios of the National Institute of General Medical Sciences (NIGMS), which provides support for fundamental research, and coordinate with other agencies such as the National Science Foundation (NSF) and the Department of Energy (DOE) to ensure that scientific opportunities in important areas of basic bacteriology physiology and genetics research are receiving adequate attention. The ASM recommends that NIH take steps such as workshops, requests for proposals and training grants to increase the infrastructure in this important area of science.
Over the past 10 years, new and emerging microbial threats have continued to challenge the research community as well as the public health infrastructure. Despite scientific and medical advances, infectious diseases persist as the third leading cause of death in the United States and the second leading cause of death worldwide. A recent report from the Institute of Medicine on microbial threats to public health concluded that a comprehensive infectious disease research agenda is essential for successful anti-disease campaigns. The basic and applied research supported by the National Institute of Allergy and Infectious Diseases (NIAID) is essential to responding to infectious disease public health challenges. Unfortunately, the budget for the NIAID would increase by only 1.3 percent in the request for FY 2006, far less than the amount needed to maintain or accelerate NIAID supported work to combat a myriad of infectious diseases.
Influenza is a familiar infectious disease threat with the proven potential for decimating pandemics. Influenza develops in about 20 percent of US citizens each year and an estimated 36,000 die annually from complications of influenza in the United States, with 250,000 to 500,000 deaths worldwide. In the United States influenza and pneumonia remain the leading infectious cause of mortality and are ranked seventh among all causes of death. Influenza viruses steadily mutate and new strains periodically move from animal hosts to humans. World attention is drawn to outbreaks of avian influenza in Southeast Asia with about 55 infected persons and 42 deaths since January 2004. The current strain of H5N1 influenza could acquire characteristics that permit transmission among humans which could lead to a worldwide influenza pandemic. The 1918 influenza pandemic killed at least 20 million people and pandemic avian influenza could kill millions of people. The NIH Influenza Genomics Project conducts rapid sequencing of the complete genomes of thousands of avian and human influenza viruses and newly emerging ones and will study the molecular basis of how new strains of influenza virus emerge and characteristics that contribute to virulence. Research is being done to develop a live attenuated vaccine candidate against each of 15 isolated hemagglutinin proteins that may speed the development of a vaccine against a potential pandemic strain. Using reverse genetics technology, a genetically engineered vaccine candidate against H5N1 was developed in weeks. This technology was also used to identify a genetic mutation in a H5N1 viral gene that makes the virus more lethal.
In late 2002, Severe Acute Respiratory Syndrome (SARS) became the first severe newly emergent infectious disease of the 21st century, but was rapidly characterized and contained. Because of air travel by its earliest victims, SARS reached five countries within 24 hours and more than 30 countries on six continents within six months of the initial diagnosed case. Nearly 8,000 persons became ill and international travel and trade were greatly affected. The global cost of SARS has been estimated at about $80 billion. NIAID funded research in collaboration with the Centers for Disease Control and Prevention (CDC) demonstrated that SARS is a viral disease and a new coronavirus was identified quickly as the causative agent. By May of 2003, an international collaboration of researchers had decoded the genetic sequence of the virus to develop a candidate vaccine that in November 2004 entered early phase tests in humans. Less than two years separated the discovery that SARS is a new infectious disease and the beginning of vaccine testing in humans, a process that traditionally can take decades. Results came quickly because of research and public health cooperation, NIAID resources and new molecular biology techniques. Research and technology developed during past disease outbreaks facilitate NIAID responses to unique or sporadic challenges like SARS, West Nile virus, Ebola virus, and bovine spongiform encephalopathy.
Research yields major insights into the pathogenic mechanisms of established diseases such as HIV/AIDS, tuberculosis and malaria. An estimated 40 million people worldwide are living with HIV/AIDS. NIAID research has made possible critical discoveries about the basic biology of HIV and the immune response to HIV infection which has led to the development of therapies that suppress the growth of the virus. Approximately 20 antiretroviral medications that target HIV have been developed and approved by the Food and Drug Administration. More scientific research is needed on the virus to identify additional targets for therapeutic interventions and vaccines. Despite the fact that tuberculosis (TB) is one of the oldest infectious diseases known, the global incidence rate is still increasing. More than one third of the world is latently infected with TB. Every day there are 5,000 deaths due to TB. A big part of the problem is the increasing number of patients with the deadly combination of TB and HIV. The only available medicines to treat and diagnose TB are from another era. Rapid development of new tools is greatly needed to address the growing problems of multi-drug resistant TB. Malaria is one of the major killers of humans in the world with an estimated 300 million acute illnesses each year and more than 1 million deaths. Both tuberculosis and malaria pathogens are increasingly resistant to commonly used antimicrobial drugs. Genomic and postgenomic techniques are being applied to identify key molecular pathways that could be exploited to develop TB interventions and vaccines. The complete genomic sequence of the malaria vector and parasite were completed in 2002, providing powerful tools to further characterize the genes and proteins involved in the life cycle of the malaria parasite. NIAID supported programs in basic and applied areas are contributing to knowledge that is needed to design new vaccines, therapeutics and diagnostics against these formidable infectious diseases that exact a terrible social, economic and human toll globally.
The NIAID research portfolio is challenged as never before to address new and emerging infectious diseases and those that have affected humans for thousands of years but are still a public health threat. NIAID supports important research on the hepatitis viruses which cause liver inflammation and tissue damage and can cause chronic infections. There are more than 25 identified sexually transmitted infections (STIs) that affect more than 15 million people in the United States. STIs can lead to infertility, complications in pregnancy, cervical cancer, low birth weight, congenital/perinatal infections and other chronic conditions and are of critical global and national health priority because of their impact on women and infants. NIAID basic and clinical research studies on mechanisms of pathogenesis of STIs and prevention strategies for the control of these infections are essential. Bacterial and viral infections of the gastrointestinal tract often lead to diarrheal disease and to chronic conditions such as ulcers and stomach cancer. In the US, diarrhea is the second most common infectious illness and diarrheal diseases account for 15 to 34 percent of deaths in some countries. Infection with Helicobacter pylori is a major risk factor for developing peptic ulcer disease, stomach cancer and primary gastric B cell lymphoma. NIAID supports research to understand, prevent and treat enteric diseases through a variety of initiatives. NIAID also sponsors research on West Nile Virus, which first emerged in 1999 in New York City, other insect-borne diseases such as Lyme Disease and fungal diseases that can cause severe systemic infections.
The NIH is responsible for the implementation of the strategic plan for biodefense research. The NIH biodefense budget, proposed at $1.7 billion for FY 2006, is part of the budget for NIAID, the lead agency at NIH for infectious diseases and immunology research. Research is the backbone of the NIAID biodefense efforts and includes genomics and studies of pathogenesis and host defense, microbial physiology and animal disease models. Sustained funding by the Administration and Congress over the past few years is making possible significant progress evidenced by over 60 NIAID biodefense initiatives now in place.
Following the September 11, 2001 terrorist attack in the United States and terrorist events using biological agents, awareness about the potential of bioterrorism and the vulnerability of people to a bioterrorism event prompted the US government to pursue a range of programs and capabilities to prepare for future emergencies (Homeland Security Presidential Directive 10). Among these was increased funding for research and development of medical countermeasures within the Department of Health and Human Services to enable the country to mount a successful medical and public health response to a biological attack on the civilian population should such a terrible event occur. In 2002 the ASM testified before Congress that pathogenic microbes pose a threat to national security whether they occur naturally or are released in a bioterrorism attack. Biodefense research is part of the continuum of biomedical research aimed at protecting the nation and the world against infectious diseases. The ASM supports having federal biomedical and infectious disease research efforts related to civilian human health prioritized and conducted by and at the direction of the DHHS and NIH.
In early 2002, the NIAID convened a panel of experts, the Blue Ribbon Panel on Bioterrorism and Its Implications for Biomedical Research, to provide guidance on the future biodefense research agenda, research resources, facilities and scientific personnel. The NIAID developed research priorities and goals for potential agents of bioterrorism with particular emphasis on the “Category A” agents considered by the CDC and NIH as the worst currently recognized potential bioterror threats. The NIAID developed the NIAID Strategic Plan for Biodefense Research, The NIAID Biodefense Research Agenda for CDC Category A Agents, and the NIAID Biodefense Research Agenda for Category B and C Priority Pathogens. Approximately 60 NIAID initiatives were funded in fiscal years 2002-2004, including funding for a network of 8 nationwide multidisciplinary Regional Centers of Excellence (RCE) for Biodefense and Emerging Infectious Diseases Research, 2 National Biocontainment Laboratories (NBLs) and 9 Regional Biocontainment Laboratories (RBLs) to provide secure space for the expanded civilian biodefense research program. The genomes of the biological agents listed as posing the most severe threats have been sequenced; new animal models have been developed to test promising drugs and repositories have been established to catalog reagents and specimens. NIAID is sponsoring basic research to understand structure, biology and mechanisms by which potential bioweapons cause disease, studies to elucidate how the human immune system responds to dangerous pathogens and technology to translate basic research into medical countermeasures to detect, prevent and treat diseases caused by potential biological weapons.
Advances in biodefense research are outlined in the NIAID Biodefense Research Agenda for CDC Category A Agents Progress Report and the NIAID Biodefense Research Agenda for Category B and C Priority Pathogens Progress Report. NIAID supported biodefense research is conducted through collaborataive efforts with academic institutions and public/private partnerships and scientific communications are open, facilitating scientific and medical progress against infectious diseases. NIAID anticipates that the large investment mandated by the government in civilian biodefense research will advance scientific knowledge that will have positive spin offs for other diseases.