Proliferation Threats from Proliferation Threats from Biotechnology:Biotechnology:

What is Dual-Use Research?What is Dual-Use Research?

Lisa DonohoeProject ManagerNonproliferation Education ProgramJames Martin Center for Nonproliferation StudiesMonterey Institute of International StudiesCreated for the Nuclear Threat Initiative Teacher’s Toolkit

Biological Dual-Use ResearchBiological Dual-Use Research

Learnodes.com/Judy Breck

“Biotechnology represents a ‘dual use’ dilemma in which the same technologies can be used legitimately for human betterment and misused for bioterrorism.”

Biotechnology Research in an Age of Terrorism, National Academy of Sciences, 2004

“…research that, based on current understanding, can be reasonably anticipated to provide knowledge, products, or technologies that could be directly misapplied by others to pose a threat to public health, agriculture, plants, animals, the environment, or materiel.”

National Science Advisory Board for Biosecurity

Peaceful Use Weapons UseDual-Use

BioweaponsStates (Iraq vs Iran)

Terrorists

BiodefensePublic Health Offensive Military

Defends against military use of bioweapons

Develops capabilities for military use of bioweapons

DiagnosticsDrugsVaccinesAntivirals

Research on the same biotechnologies

AP/Wide World Photo/Department of Defense

A suspected mobile biological weapons facility in Iraq.

Canadian Institutes of Health Research

U.S. Army Medical Research Institute of Infectious Diseases

Peaceful Use Weapons UseDual-Use

BioweaponsStates (Iraq vs Iran)

Terrorists

BiodefensePublic Health Offensive Military

DiagnosticsDrugsVaccinesAntivirals

Research on the same biotechnologies

AP/Wide World Photo/Department of Defense

A suspected mobile biological weapons facility in Iraq.

Canadian Institutes of Health Research

U.S. Army Medical Research Institute of Infectious Diseases

Potential for diversion to

offensive military use

Who Does This Research?Who Does This Research?

• Military– e.g. U.S. Army Medical Research Institute of

Infectious Diseases – USAMRIID

• Government – e.g. Centers for Disease Control, Atlanta

• Private companies (commercial)– e.g. Amgen (20k employees)

• Academia– e.g. Boston University, University of California, Johns

Hopkins University

Proliferation Risks of Dual-Use Proliferation Risks of Dual-Use ResearchResearch

• Categories of risk– Technologies that deliver beneficial drugs to

the body could be used for weaponizing biological agents

– Research could have unintended consequences

– Dangerous agents could be released accidentally from the lab through infected personnel

– Research results can be published in easily accessible journals and on the Internet

– Knowledge or techniques could help to create “novel” pathogens with unique properties or create entirely new classes of threat agents

– Dangerous agents could be stolen or diverted for non-peaceful purposes

IRRI Images

Examples of RiskExamples of RiskPotential Weaponization of New TechnologiesPotential Weaponization of New Technologies

• 1997: Dr. David Edwards, then at Pennsylvania State University, developed a way to deliver aerosolized medicine using large porous carrier particles.

• The method dramatically increased the amount of drug that made it deep into the lungs, providing a revolutionary treatment for conditions like asthma.

• After the anthrax attacks of 2001, its dual-use implications became clear: This technology could be used to intentionally deliver inhalation anthrax in a superior way.

• His research appeared in Science, bringing into question whether someone could use the information for weaponizing anthrax and other aerosolized agents.

See: Dual Use Research in Aerosol Drug Deliverywww.fas.org

Federation of American Scientists

Dr. David A. Edwards, Harvard University

Examples of RiskExamples of RiskUnintended Consequences of Genetic EngineeringUnintended Consequences of Genetic Engineering

• Australian grain industry suffered millions of dollars in damage to crops by infestations of mice

• Australian researchers genetically altered mousepox, an infectious virus that affects mice, to induce sterility in the mice

• The researchers inadvertently produced a recombinant virus with greatly increased lethality

• The virus killed laboratory mice, both those with genetic resistance to the virus and those mice immunized against it

• Their paper was published in the Journal of Virology in 2001, leading to concern that the same technologies could be used to weaponize smallpox and other pox viruses that affect humans

• These weaponized viruses would be more lethal and resistant to vaccines

“one step away from the ultimate bioweapon”Rachel Nowak, New Scientist Online News

Examples of RiskExamples of RiskAccidental Exposure of Laboratory PersonnelAccidental Exposure of Laboratory Personnel

• 2005: Three Boston University researchers became ill after being exposed to tularemia, a highly lethal pathogen

• Two researchers became ill in May and a third in September, but their illnesses were not linked to tularemia until October. The cases were not reported until November.

• Tularemia is not transmitted from human to human, but the lab was seeking approval to study anthrax, plague, and other highly infectious deadly pathogens.

• The scientists believed they were working with a research strain that would not cause illness, but a highly infectious strain was accidentally mixed with the harmless variety.

• The researchers also violated biosafety procedures that required them to work with tularemia inside an enclosed box, called a hood, that sends air through sophisticated filters.

• "The assurances that BU has given that it can maintain perfect control of these facilities are called into question," said Philip Warburg, leader of Conservation Law Foundation.

Stephen Smith, Boston Globe, January 19, 2005

Examples of RiskExamples of RiskNovel Microorganisms andNovel Microorganisms and Synthetic BiologySynthetic Biology

• The Synthetic Biology Working Group at M.I.T. is attempting to engineer a set of genetic building blocks called “BioBricks,” short pieces of DNA with functional genetic elements – A BioBrick sends and receives biochemical signals to be cut and pasted

into a linear sequence of other BioBricks, like pieces in a Lego set• Goal: to convert bioengineered cells into tiny programmable

computers• Bioengineered microorganisms (and possibly other life forms) could

potentially produce pharmaceuticals, detect toxic chemicals, break down pollutants, repair defective genes, and destroy cancer cells

• These functions could also potentially be used for intentional, malevolent purposes

• Synthetic microorganisms with new, poorly understood, “emergent properties” could be accidentally released from the laboratory, possibly spreading into new ecological niches and causing the evolution of novel and potentially harmful characteristics

“The Promise and Perils of Synthetic Biology”Jonathan B. Tucker and Raymond A. Zilinskas

Biodefense ResearchBiodefense Research

• Carried out in government and private laboratories

• Research on “select agents”— “bioterrorism” agents that cause highly infectious diseases and are attractive for bioterrorism

• Research intended to help defend against use of these agents as weapons

• Dual-use: agents, techniques, and technologies developed can also be used for malicious purposes

Biodefense Spending Increase Biodefense Spending Increase Since 9/11Since 9/11

• "We have spent or requested nearly $19.2 billion since September 11, 2001." Secretary of Health and Human Services Mike Leavitt

• In 2005 estimated combined spending for civilian biodefense by 7 federal departments and agencies: $7.647 billion, approximately 18 times more than FY 2001 outlays of $414 million. Research analyst Ari Schuler, University of Pittsburgh Center for Biosecurity

Barton Reppert, The Biodefense Buildup: Fallout for Other Research Areas? Washington Watch, April 2005, http://www.aibs.org/washington-watch/washington_watch_2005_04.html

What Led to Increase in What Led to Increase in Biodefense Spending?Biodefense Spending?

• 2001: Letters containing anthrax spores were sent to politicians, news agencies, and newspapers.

• The letters were sent over the course of several weeks.

• Five people died and 17 were infected.

• Together with the 9/11 attacks, fear of terrorists using biological weapons led to a massive buildup of the biodefense industry

Examples of RiskExamples of RiskAnthrax: Stolen or Diverted?Anthrax: Stolen or Diverted?

• 2008: A U.S. Army Medical Research Institute scientist, Dr. Bruce Ivins, committed suicide after the FBI suspected him of diverting anthrax spores from his research lab and using them in the 2001 anthrax letter attacks.

• Dr. Ivins began showing signs of mental illness and taking anti-depressants in 2000, and the FBI had known that the anthrax used in the attacks came from his lab since 2005. Yet he was allowed to work at the highly sensitive research lab until November 2007.

• Dr. Ivins had worked on an experimental vaccine to treat anthrax. After the attacks, his work led to a proposed $877 million federal contract, though the deal fell through two years later.

• The FBI claimed that a preponderance of circumstantial evidence led to him, and the strain of the anthrax used in the letter attacks matched the anthrax in his laboratory.

• After Dr. Ivins committed suicide, the FBI case was closed, leaving his guilt inconclusive.

Anthrax spores

Dr. Bruce Ivins

Risks of BiodefenseRisks of Biodefense

• Increasing stocks of highly dangerous diseases such as anthrax, tularemia, and botulism (“select agents”)

• Increasing number of high-containment facilities– Biosafety Levels (BSL) 2, 3, 4

(highest risk)• Increasing number of new, less

experienced researchers and student researchers– Higher risk of accidents, diversion

• Increasing risk of accidental release, theft, diversion, and creation of novel agents

BSL-4 Laboratory

CDC Classification of Select CDC Classification of Select AgentsAgents

• Category A: • Anthrax (Bacillus anthracis)• Botulism (Clostridium botulinum toxin) • Plague (Yersinia pestis) • Smallpox (Variola major) • Tularemia (Francisella tularensis) • Viral hemorrhagic fevers (filoviruses [e.g., Ebola,

Marburg] and arenaviruses [e.g., Lassa, Machupo])

• Category B (partial list)• Brucellosis (Brucella species) • Food safety threats (e.g., Salmonella species, E.

coli)• Glanders (Burkholderia mallei)• Melioidosis (Burkholderia pseudomallei)• Q fever (Coxiella burnetii) • Ricin toxin from Ricinus communis (castor beans)• Staphylococcal enterotoxin B• Viral encephalitis (e.g., Venezuelan equine

encephalitis)• Water safety threats (e.g., Vibrio cholerae)

• Category C • Emerging infectious diseases such as Nipah virus

and hantavirusCenters for Disease Control and Prevention,

Department of Health and Human Services

Anthrax DNA, in a gel electrophoresis plate, fluoresces under ultraviolet light. Kevin N.

Roark, Public Affairs, Los Alamos National Labs

Brucellosis Culture

Minnesota Department of Health, Infectious Disease Epidemiology, Prevention, and Control Division

More high-containment biolabs in dense population areas, like cities and universities; more people with access to bioterror agents; more secrecy about biodefense activities

More, Less ExperiencedMore, Less ExperiencedResearchersResearchers

Pathogen Total Number of Principal Investigators 2001-2005 YTD

Number of those PIs that received NIAID Funding for Agent before 2001

Percentage Never before Funded by NIAID for Agent

Anthrax 219 6 97.3% (213) Brucellosis 6 0 100% (6) Glanders 10 1 90% (9) Plague 107 6 94.4% (101) Melioidosis 16 0 100% (16) Tularemia 81 2 98% (79) TOTAL 439 15 96.6% (424)

The NIAID Newbies: How Expert are They?One Measure of Pathogen-Handling Experience

The Sunshine ProjectNIAID = National Institute of Allergy and Infectious Diseases

Summary:Summary:Proliferation Risks of BiotechnologyProliferation Risks of Biotechnology

• “Creating a bioweapon requires the skills and materials to handle and grow agents, isolate, and disseminate them.

• Any medical advance that improves the ease of engineering, handling, or delivering treatment has the potential to be applied by those wishing to do harm and can be considered ‘dual-use.’

• Each year hundreds of dual-use research articles are published, making them accessible to any member of the research community.

• Thousands of pieces of scientific equipment are purchased on the Internet.

• This openness creates the risk that available information, reagents, or equipment will be used to create more dangerous biological weapons.”

Dual Use Research in Aerosol Drug Deliverywww.fas.org