Major Trends in Biomedical Research

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Bioethics and Biodefense
Enhance a culture of responsibility for proactive
research to counter potential biological threats
and emerging infections diseases
Achieving Acquisition Excellence
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Expectations
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Bioterrorism - a real and present dangerAnthrax
attacks in the United States, 2001
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Research Impacts from Attacks

• Awareness
• Cultural responsibility
• Broaden - researchers and infrastructure
• Advance research practical issues
• Advances innovation in research new technology
• New methods of detection, treatment, prevention
• Ability to respond to threats quicker
• having access to sequence of pathogens
  structures of proteins and shared data with new
  knowledge discovery and other software tools.
• Restricted publications classified research
• Dual use research
• Improve public health

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Topics for Discussion

• How quickly have we responded?
• Coordination Planning Funding - Results
• What is the relative threat?
• Emerging Microbes and Biothreats
• Genetically altered and dual use research
• natural accidental malicious
• How do we guide dual use research?
• Why is NIAID doing research to protect against
  radiation exposure?

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How Quickly Have We Responded
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Biodefense Complementary Roles within DHHS
Coordinating Role of OASPHEP
O A S P H E P
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Release of BioShield Funds

• Interagency Approval of Requirement
• Findings by Secretaries of DHS and HHS
• Determination of material threat
• Suitability of countermeasure
• No significant commercial market
• Numbers of doses required and cost
• Approval by the President

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NIAID Responded Immediately
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Let Us Recognize Acquisition Staff
Program Staff
Contracts Grants Staff
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President Bush Visits the NIAID Vaccine Research
CenterFebruary 4, 2002
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Current Countermeasures
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Development of New Countermeasures
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Topics for Discussion

• How quickly have we responded?
• Coordination Planning Funding - Results
• What is the relative threat?
• Emerging Microbes and Biothreats
• Genetically altered and dual use research
• natural accidental malicious
• How do we guide dual use research?
• Why is NIAID doing research to protect against
  radiation exposure?

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Understanding Microbial Threats
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Imagine 1 Human Cell
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Pitcher's Mound 1 Bacteria
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Microbes Emerging Diseases and Bio-threats

• Bacteria
• Viruses
• Toxins

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NIAID is a Global Organization
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NIAID Responds to Emerging Health Needs
(examples)

• West Nile Virus
• Use of biological agents in terrorist attacks

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West Nile Virus An Example
Human
Animal
Source CDC Sept. 2002
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West Nile Virus An Example
Human
Animal
Source CDC Sept. 2002
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West Nile Virus An Example
Human
Animal
Source CDC Sept. 2002
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West Nile Virus An Example
Human
Animal
Source CDC Sept. 2002
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West Nile Virus - 2003 An Example
Human
Animal
Source CDC Sept. 2002
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As of Today for 2004 2151 Cases 68
Deaths
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Topics for Discussion

• How quickly have we responded?
• Coordination Planning Funding - Results
• What is the relative threat?
• Emerging Microbes and Biothreats
• Genetically altered and dual use research
• natural accidental malicious
• How do we guide dual use research?
• Why is NIAID doing research to protect against
  radiation exposure?

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Microbes Are Genetically Modified by

• A natural event
• Unintended result of experiments
• Malicious manipulation

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Resistant bacterial infections a public
health problem with global security implications
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Microbial Development of Resistance Natural Event
Antimicrobial drugs in the environment pressure
microbes to develop resistance
Chromosomal mutations transpositions
MICROBE
Extra-chromosomal plasmid acquisition
RESULT Development of drug-resistant strains
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Malicious Manipulation
Not easy

• Pathogenicity or other characteristics, such as
  stability, may be compromised when multi-drug
  resistance is deliberately engineered.
• Soviet researchers failed to design
  environmentally stable virulent
  multi-drug-resistant strains of tularemia
  plague.

but still a concern
Designing new or modified virulent pathogens
that could evade drugs current vaccines may be
possible with new, sophisticated technologies.
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Malicious Manipulation Potential Impact

• Drug resistance
• Virulence
• Environmental stability
• Dissemination potential
• Ease of Replication
• Ability to Detect
• Effectiveness of Countermeasures

Note Possibility of new chimeric organisms
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Topics for Discussion

• How quickly have we responded?
• Coordination Planning Funding - Results
• What is the relative threat?
• Emerging Microbes and Biothreats
• Genetically altered and dual use research
• natural accidental malicious
• How do we guide dual use research?
• Why is NIAID doing research to protect against
  radiation exposure?

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NRC Report on Dual Use Research
Report of the National Research Council of the
National Academies Biotechnology Research in
an Age of Terrorism Confronting the Dual Use
Dilemma (October 2003)
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NRC Criteria for Experiments of Concern

• Demonstrate how to render a vaccine ineffective
• Confer resistance to therapeutically useful
  antimicrobials
• Confer pathogenicity or enhance the virulence of
  a pathogen
• Increase transmissibility of a pathogen
• Alter the host range of a pathogen
• Enable evasion of diagnostic/detection modalities
• Enable weaponization of a biological agent or
  toxin

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Gene Mutation Leads to Super-Virulent Strain of
TBUC Berkeley Press December 9, 2003

• Disabling a set of virulence genes led to a
  more deadly form of TB
• Results were completely unexpected

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Bioterror Researchers Build a More Lethal
MousepoxNew York Times November 1, 2003

• Gene that suppresses immune system added to
  mousepox virus (close relative to smallpox)
• Killed all mice, even vaccinated ones or those
  treated with antivirals
• A combination therapy was protective
• Effort to learn how to combat genetically
  engineered smallpox

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Synthetic Polio Virus Made from Mail-Order
KitsCELL July, 2002

• Scientists synthesized entire polio genome using
  readily available reagents and well-established
  molecular biology techniques
• Synthetic virus was infectious, capable of
  replication, and pathogenic.
• In vitro synthesis took 3 years to complete
• Application could lead to benefits for medicine,
  such as rebuilding other viruses in a weakened
  form to help devise vaccines.

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Nature News November 14, 2003
Virus Built from Scratch in Two WeeksNew
method accelerates prospect of designer microbes

• Scientists made Phi-X virus, a harmless
  bacteriophage, in 2 weeks from commercially
  available ingredients
• Virus was fully functional
• New method a step toward new lifeforms to clean
  up toxic waste, secrete drugs, produce fuel

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Life Science Research National Biosecurity
Initiatives

• USA PATRIOT Act of 2001
• Public Health Security and Bioterrorism
  Preparedness and Response Act of 2002
• Agricultural Bioterrorism Protection Act of 2002
• Promoting and conducting research on the
  development of countermeasures for biologic
  threats
• Establish the National Science Advisory Board for
  Biosecurity (NSABB)

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Links in the Infrastructure and the Basic and
Clinical Research Agenda

• To defend against a terrorist biological attack
  and an emergent infectious diseases

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Topics for Discussion

• How quickly have we responded?
• Coordination Planning Funding - Results
• What is the relative threat?
• Emerging Microbes and Biothreats
• Genetically altered and dual use research
• natural accidental malicious
• How do we guide dual use research?
• Why is NIAID doing research to protect against
  radiation exposure?

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Links in the Infrastructure and the Basic and
Clinical Research Agenda

• To defend against a terrorist biological attack
  and an emergent infectious diseases
• To help against a radiological attack and
  understanding and enhancing the immune system to
  recover from radiation exposure or treat diseases

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Rad/Nuc Event Planning Challenges

• Dirty bomb
• Small affected population
• Low level exposure
• Limited tools for isotope identification,
  dosimetry
• Long-range susceptibility to cancer
• Small scientific community
• Improvised nuclear device attack on nuclear
  facility
• Large affected population
• High level exposure
• Acute radiation syndrome, blast injuries,
  hematopoietic and GI syndromes
• Triage vs. medical care treatment pre- or
  post-exposure

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• Today, terrorist organizations have access to
  nuclear material which could produce a crude
  weapon with a yield of 0.01 kt to 20 kt in
  size.
• Hiroshima 12.5 kt

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Health Consequences of a 1 kt Nuclear Bomb (4 Gy
exposure zone)

• 1 Gy Nausea and vomiting in 10 within 48 hr of
  exposure
• 2 Gy Nausea and vomiting in 50 within 24 hr of
  exposure marked decrease in WBC and platelet
  counts
• 4 Gy Nausea and vomiting in 90 within 12 hr,
  diarrhea in 10 within 8 hr 50 mortality in the
  absence of medical care
• 6 Gy 100 mortality within 30d in the absence of
  medical care, due to BM failure

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Americans see health as integral to national
security, and the need for a strong federal
investment in public health and saftey
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Key Examples
Emerging Diseases
Biodefense

• Acute to Chronic Conditions

Aging Population
Health Disparities
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NIH
Supporting Discovery to Improve Human Health
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Thanks For Your Time Questions - Comments