Breakthroughs in Bioscience

Breakthroughs in Bioscience From NIH-Funded Basic Research to Improved Health Connecticut

National Institutes of Health (NIH) • Nation’s medical research agency • Funds the science that leads to medical advancement • Campus in Bethesda, MD – but most funding is distributed to university researchers throughout the United States • In FY 2011, Connecticut received almost $477M in NIH funding

Research Is Critical to Connecticut’s Economy • Connecticut bioscience currently employs more than 18,000 people and spends over $6B on operations annually within the state • Research at the University of Connecticut (UConn) and the University Health Center (UCHC) creates more than 5,113 jobs and adds almost $400M in economic output per year • Pharmaceutical companies with operations in CT spent more than 25% of their worldwide R&D expenditures in the state

Leveraging the State’s Investment with Extramural Research Dollars • Connecticut Innovations (CI) was created by the state legislature in 1989 and has become the state’s leading risk capital investor • Between FY1995 and FY2005, CI leveraged its initial $65M capital contribution from the state into a total of $124M of total capital to support various initiatives • Connecticut has an R&D tax credit exchange that allows companies to receive 65 cents on the dollar out of their research and development tax credit, encouraging start-up companies to establish in CT

NIH: Saving Lives Through Science • Current annual budget (FY2012) of around $30.6B • Greater than 80% distributed throughout the country • Almost 50,000 grants • More than 325,000 scientists at over 3,000 research sites • How much money is being spent in your local area? • http://report.nih.gov/award/organizations.cfm • Portfolio of basic, translational, and clinical research NIH has been involved in nearly all the major medical & health related discoveries of the past fifty years

How NIH Makes Science Happen… • Most researchers working at local universities, hospitals, and research institutions are dependent on federal support to fund their research, hire lab personnel, and train young scientists • Researchers write grant proposals to compete for funding • Must explain why they think it’s a good idea, how they’re going to do the experiments, and what impact it will have on science and medicine • Proposals are reviewed in a two-tier system • Peer-reviewed by scientists to ensure highest quality science • Reviewed again for applicability to scientific or health priorities, by NIH officials and other stakeholders, including public members • NIH review system is the envy of the world! • Very competitive! • Only 1 in 4 proposals funded in the 2008 fiscal year • Lots of high quality research not being done for lack of funding

Basic Research: From Bench to Bedside • A portion of NIH funding goes to basic or fundamental research • Basic research is driven by interest in a scientific question • The main motivation is to expand knowledge and understanding • However, the insight into how the human body works and understanding of how diseases and disorders operate provides the foundation for medical progress "People cannot foresee the future well enough to predict what's going to develop from basic research. If we only did applied research, we would still be making better spears." Dr. George Smoot, Berkeley National Lab

What About Medical Breakthroughs? • Medical breakthroughs often come from unrelated areas of science or medicine • Research on cancer biology has led to drugs for heart disease, osteoporosis, and viral diseases like influenza, herpes & AIDS • Physicists studying the effects of magnets on atomic particles made the discovery that gave us magnetic resonance imagining (MRI) • It often takes years or decades of fundamental knowledge to solve or find different pieces of the puzzle • This makes it difficult to predict where the next breakthrough will come from • Makes it imperative to support a broad range of scientific research • Too risky for the private sector, federal funding is critical for research

Evolution of Research to Healthcare Some recent examples…

Cardiovascular Disease • Information on the biochemical structure and synthesis of cholesterol led to the development of statins, a class of drug used to lower cholesterol • Discoveries in basic kidney biology and an increased understanding of the molecular regulation of blood pressure converged with an unexpected finding involving snake venom to give us ACE inhibitors, one of our most effective hypertension medications • Research into the mechanism of how blood forms clots, together with the search to find a new cancer treatment and the first commercial use of recombinant technologies, resulted in rt-PA, a clot-busting drug that can prevent death from heart attack or stroke

Results of Cardiovascular Disease Research CVD disease death rates(United States: 1900-2006) “Americans can expect to live an average of four years longerdue to the reductions in deaths due to cardiovascular disease, largely as a result of NIH research.”

Future Directions… • Genome-wide associations studies (GWAS) are providing unprecedented insight into the intricate role genetics plays in the development of heart disease and identifying possible targets for novel drug therapies • Research on the effect of air pollution on blood vessel constriction is helping scientists understand how environmental factors effect cardiovascular health • Innovative imaging systems are being developed to allow for simultaneous evaluation of electrical activity and metabolic properties in the heart, allowing for the study of the complex mechanisms which lead to sudden cardiac arrest

HIV / AIDS • Fundamental knowledge of how viruses replicate gave scientists targets for therapy that led to the discovery of a way to block replication, resulting in the development of azidothymidine (AZT) • Increased understanding of how HIV operates at the cellular and molecular level identified more targets, and eventually led to the combination of drugs knows as the ‘triple cocktail’

Results of HIV / AIDS Research The number of cases has remained relatively stable while the number of deaths has decreased AIDS has been transformed from an acute, fatal illness to a chronic, manageable condition

Future Directions… • Topical antimicrobial products, or microbicides, offer one of the most promising avenues to primary prevention of HIV transmission • A number of HIV vaccine clinical trials have begun, which depend on fundamental research of the human immune response and on understanding of the way in which HIV infects cells • Investigators have identified the existence of HIV reservoirs that persist despite antiretroviral therapy, and efforts are now being focused on understanding and eliminating these reservoirs

Cancer • The discovery that estrogen’s role in breast cancer, together with basic research into the shape and characteristics of the estrogen receptor, gave us tamoxifen, which can reduce breast cancer incidence among women at risk by over 45% • The breakthrough finding that human papillomavirus (HPV) could cause cervical cancer led to a new vaccine that NIH estimated could reduce cervical cancer incidence by as much as 90% • While investigating the cellular machinery controlling cell growth, scientists found the 26S proteasome, the inhibition of which is the power behind bortezomib – now used to treat patients with multiple myeloma

Results of Cancer Research “Overall cancer survival rates have improved significantly, from about 50% in the 1970’s to 66% in recent years. This is due, in part, to both earlier detection and advances in treatment.”

Future Directions… • Medical researchers have found certain antibodies that are present only in tumors and may enable early detection and diagnosis of certain cancers • The Cancer Genome Atlas (TCGA), a project dedicated to accelerating our understanding of cancer genetics, has enabled deeper understanding of the most common form of adult brain cancer, glioblastoma multiforme • By suppressing the action of a certain cellular receptor,CD47, researchers have developed a method to protect healthy tissue from radiation therapy while making cancerous cells more vulnerable

Infant Mortality • Research on the fundamental biology of lung function enabled the discovery of surfactant, a protein crucial for survival of premature infants, and enabled a decrease in the number of infant deaths from respiratory distress from 15,000 per year to less than 1,000 by 2002 • The use of anti-virals to prevent mother-to-child HIV transmission reduced the rate from 25% to nearly 1% • Studies on a metabolite of progesterone led to the finding that injections of this compound, progesterone 17P, could prevent pre-term delivery by as much as 30%, which is particularly significant in African American women

Results of Research on Infant Mortality In less than a century, infant mortality in the United States has been reduced by 90% This translates to almost 500,000 babies saved per year

Future Directions… • In order to better diagnose and treat congenital heart defects, a leading cause of infant mortality, scientists are developing new non-invasive imaging technologies for prenatal heart studies • Novel diagnostic techniques for amniotic fluid infection, a major risk factor for preterm birth, are being developed based on a recent finding that bacteria in the amniotic cavity can form biofilms (which make infections harder to detect)

Neural Prosthetics • The groundwork for neural prosthetics was laid by more than a century’s worth of basic research by anatomists, biochemists, and electrophysiologists • The first cochlear implant was introduced in the 1970s; today, more than 23,000 adults and 15,000 children in the U.S. owe their hearing to this device • The artificial retina is delicate enough not to damage the eye yet complex enough to provide visual input to the human brain; by 2011, the research team expects to start clinical testing on a version that enables reading and facial recognition

Urgent Need for Prosthetics Research and Development • Body armor saves lives, but provides little to no protection for a soldier’s limbs • One of the major impairments seen in veterans returning from Iraq and Afghanistan is amputations

After amputation, the nerves controlling the missing limb remain active Scientists have developed superfine electrode arrays to connect these nerves with prosthetic limbs This will allow amputees to control and sense their prosthetics intuitively, making them feel more like their original limbs Future Directions…

NIH-Funded Discoveries at Yale • The first use of chemotherapy as a cancer treatment was performed in 1942 at Yale School of Medicine • Scientists discovered why proteins fold properly, leading to treatment for diseases such as Alzheimer’s, Huntington’s, and Parkinson’s • Creation of the first insulin pump • Identified Lyme disease and the genes responsible for high blood pressure, osteoporosis, dyslexia and Tourette’s syndrome • Researchers determined that digoxin therapy for heart failure had different effects in women than in men • Investigators determine that falling, previously considered a consequence of aging, is a diagnosable health condition that is the result of multiple impairments and diseases acting together

The Bottom Line… • People are living longer, healthier lives because of NIH funded medical research • What were once swiftly fatal illnesses have become treatable or manageable conditions • For those suffering from diseases that have no current treatment or cure, medical research provides hope

The Challenge… • NIH funding requires congressional support • Sustainable budget growth is needed to achieve the full promise of medical research • Strong, outspoken champions for NIH in Congress and within the Administration are essential Diminished investment in NIH = loss of talented researchers = missed opportunities = delays in medical progress

Connecticut’s Members of Congress Need to Advocate for NIH Funding • Nothing should surpass improving our health as a national priority • Opportunities for discoveries that translate to improved health for our citizens have never been greater • Yale consistently ranks in the nation’s top universities for research funding

We Need your Help:Working Together for NIH • Contact Senators Lieberman and Dodd, or the Congressional Representative for your district • Let them know that medical research is important to you and what a bargain it is • Write a letter to the newspaper and talk to your friends • Help educate policymakers and neighbors about the important work NIH is doing • Nothing is more important than our health • The National Institutes of Health (NIH) should be an American priority

Want to Know More? Please visit opa.faseb.org

Breakthroughs in Bioscience