Hynes CAP

Progress and Challenges in Life Sciences & Biomedical Research : 

Progress and Challenges in Life Sciences & Biomedical Research Richard Hynes, PhD, FRS Daniel K. Ludwig Professor for Cancer Research, MIT Investigator, Howard Hughes Medical Institute Presentation to the Center for American Progress October 5, 2006

The Yield from NIH-Funded Basic Research: 

The Yield from NIH-Funded Basic Research Enormous advances in understanding of biology Improvements in our Nation’s health Development of a whole new biotechnology industry Greatly improved ability to tackle new and ongoing biomedical challenges the continuing scourge of cancer the alarming increase in obesity and type II diabetes diseases of aging - Parkinson’s, Alzheimer’s, Macular degeneration (blindness) emerging infectious diseases (AIDS, SARS, avian flu) the threat of bioterrorism

Slide3: 

Age-Adjusted Death Rates: Actual and Expected United States, 1950-2000 500 400 300 200 100 1950 1960 1970 1980 1990 2000 Deaths per 100,000 ~ 514,000 Actual Deaths ~ 1,329,000 Projected 815,000 Deaths Prevented in 2000 Source: NIH/E.Zerhouni Coronary Heart Disease ~ 407,000 Projected 200 100 50 150 1950 1960 1970 1980 1990 2000 ~ 166,000 Actual Deaths 241,000 Deaths Prevented in 2000 Stroke Statins to lower blood cholesterol t-PA as a “clot buster” - agent to dissolve thromboses These drugs were firmly based on NIH-funded BASIC research into cholesterol metabolism and blood coagulation Also, importantly, changes in behavior (smoking, diet, exercise)

Slide4: 

Reasons for the Decreased Mortality from HIV/AIDS Drugs targeting the HIV Viral Enzyme - Reverse Transcriptase Drugs targeting the ability of HIV to process its own proteins These drugs were firmly based on NIH-funded basic research into other viruses - long before HIV emerged as a threat New and Emerging Infectious Diseases The source of the anthrax attack and the origin of the SARS epidemic both rapidly identified Rapid DNA sequencing technology developed for the Human Genome Program Why/How?

The Human Genome: 

The Human Genome An Encyclopedia in 23 volumes (chromosomes) - total number of letters is 3 billion Each of us has two Editions with minor differences between them Each volume (chromosome) has many different chapters (genes) - there are about 25,000 chapters (genes) in total Each chapter/gene carries a meaning/consequence - we need to understand those meanings/consequences - and the significance of “typos” We have methods to detect the minor differences between editions - we need to find out what they mean This genomic information is a goldmine - we should mine it!

Other Major Research Advances: 

Other Major Research Advances Recombinant DNA and its diverse applications tools for discovery tools for diagnosis and therapy Monoclonal antibodies Genomic medicine Recognition that all organisms use similar genes and mechanisms - “the unity of life” Mouse (and other) models of human diseases Advances in understanding brain function Neuroscience is one of the next great frontiers

Rationally Designed Anti-Cancer Drugs: 

Rationally Designed Anti-Cancer Drugs We now know many of the initiating events in cancer We can study the relevant molecules in detail That information informs drug design no longer blind screening for toxic drugs designed drugs are more specific fewer side effects Recent years have yielded several such drugs Given adequate research support, the next few years will yield many more

Recent Novel Anti-Cancer Drugs: 

Recent Novel Anti-Cancer Drugs Herceptin - a humanised monoclonal antibody against a breast cancer oncogene Current drugs target only a small number of genes/proteins There are ~25,000 genes out there to target and exploit ! Rituxan - a monoclonal antibody that targets lymphoma cells also showing promise against autoimmune diseases Gleevec / Imatinib - a drug targeting a leukemia oncogene also effective against some other cancers Avastin - an antibody that blocks tumor angiogenesis

Biotechnology Growth in the US: 

Biotechnology Growth in the US

Major Swiss Pharmaceutical CompanyRelocates to Cambridge MA: 

Major Swiss Pharmaceutical Company Relocates to Cambridge MA

Healthcare Challenges: 

Healthcare Challenges Continuing Health Issues Cancer remains a leading cause of death and illness ( ~ 1 in 3 people) Infectious diseases such as tuberculosis and malaria Emerging Health Issues Obesity (up to 15% of children and adolescents) Diabetes (Incidence of type II diabetes has doubled) Age-related Diseases, e.g., Alzheimer’s, Parkinson’s, Macular Degeneration, Inflammatory Diseases (eg Arthritis) New Threats New Health Threats (West Nile, SARS, Avian flu, Others) Biodefense The opportunites for tackling these problems have never been better Given adequate, stable support, solutions to these problems can be found

The Way Forward: 

The Way Forward Creating Revolutionary Methods of Research Mastering Complex Biological Systems Developing Multidisciplinary Scientific Teams Combining physical, mathematical and biological sciences Understanding the brain Vaccine development Re-engineering Clinical Research Exploiting the Human Genome sequence - making the most of the “goldmine”

The Awesome Potential of Stem Cellsand Regenerative Medicine: 

The Awesome Potential of Stem Cells and Regenerative Medicine Both adult (probably restricted potential) and embryonic (certainly multi-potential) stem cells offer enormous prospects for use in regenerative medicine! Bone Marrow Transplants - already in use for restoring blood cell production - e.g. after cancer therapy Juvenile Diabetes - replacement of b cells of pancreas Muscular Dystrophy - replacement of degenerating muscle cells Parkinson’s Disease - replacement of degenerating neurons Lou Gehrig’s Disease - replacement of motor neurons Spinal Cord Injuries - replacement of motor neurons

Generation of Motor Neurons from Embryonic Stem (ES) Cells: 

Generation of Motor Neurons from Embryonic Stem (ES) Cells Motor neuron precursors derived from mouse ES cells injected into chicken embryo spinal cord develop into motor neurons. Chicken motor neurons Mouse motor neurons Wichterle, Jessell et al Cell 110:385-397 (2002)

What will it take to Exploit the Current Momentum in Biomedical Research?: 

What will it take to Exploit the Current Momentum in Biomedical Research? Continued Stable Support for Innovative Research New People and Ideas - EDUCATION!! TRAINING!! Interdisciplinary Training Support for the new generation of scientists Development of new Infrastructures Structural Biology, Proteomics, Imaging, etc Libraries of genes, cDNAs and chemicals - databases Bioengineering Clinical Trials We have an unparalleled opportunity to develop radical new approaches to human health and safety It would be a tragic waste not to seize this opportunity

Related Policy Issues: 

Related Policy Issues Need for better education - K-12/college/university Insulation of science education from faith-based opposition Better communication of scientific issues to the public and to policy makers Evidence-based decision-making Recruitment of strong scientific leaders to public service Better distribution of health care and treatment More equitable distribution More cost-effective delivery Aging of the population Prevention research and education Ecological degradation Restore image of the US as the scientific culture of the future and as a humane and generous society