In cooperation with six Habitat for Humanity affiliates from all over the U.S. and experts at the Florida Solar Energy Center (FSEC), Pacific Northwest National Laboratory (PNNL), and Lawrence Berkeley National Laboratory (LBL), FAS has created The High Performance Building Guide for Habitat for Humanity Affiliates.  Funded by the Building Technologies Program at the U.S. Department of Energy, the goal of this Guide is to provide Habitat’s construction partners (called affiliates) with the knowledge, resources, and basic background to make educated decisions about improving their building practices, materials and technology choices, and decision-making and planning processes.

Targeted to the needs of the Habitat for Humanity building community, this Guide features profiles and case studies of excellent Habitat affiliates, practical recommendations and steps for improving building practices and decisions, and guidance on obtaining the partners, education, and resources necessary to make the transition to higher performing housing.

Get the High Performance Building Guide on the FAS website here.

To learn more about the Guide and to read a synopsis of its contents, check out the new Earth Systems Program blog.

BARDA was established within HHS to manage the procurement and development of medical countermeasures, such as vaccines, drugs, and diagnostic tools, for biological, chemical, radiological, and nuclear agents, as well as for other public health emergencies, such as pandemic influenza and emerging infectious diseases. BARDA’s Strategic Science and Technology Division identifies and selectively funds research and technology that will improve the effectiveness and shorten the time and cost of medical countermeasure development. The innovative technologies awarded have all demonstrated success in late-stage clinical development for countermeasures against pandemic influenza and anthrax, two prevalent diseases of concern in public health and biosecurity.

Contracts were awarded to the following organizations to continue development: the Program for Appropriate Technology in Health (PATH), the Infectious Disease Research Institute (IDRI) in Seattle, VaxDesign Corp. in Orlando and Pfenex Inc. in San Diego. A collective total of $24.6 million is allotted for initial phases and up to $53.6 million over three years.

PATH and IDRI, two global health non-profit organizations based in Seattle, Washington, were each awarded contracts for their work in ”…formulation chemistry, protein stabilization, and vaccine delivery technologies.” The two organizations entered into a Research Collaborative Agreement in June 2010 to “evaluate novel adjuvants for their ability to enhance the immune response of pandemic influenza vaccines in development.” PATH has discovered multiple strategies to extend the shelf-life of influenza vaccines for use in stockpiling or international shipping. IDRI, a biotechnology institute, will develop formulations for immunologic and cross-protection adjuvants (a drug-modifying/enhancing agent) to enhance the recipient’s immune response to the influenza vaccine and to protect against multiple novel strains that may emerge. The joint collaboration will bring the new technologies together to create a flu vaccine that is more cost-effective, affordable, and accessible on a global scale.

VaxDesign, a corporation that develops, manufactures, and markets in vitro models of the human immune system, was awarded the third contract for its work in “… technologies to accelerate evaluation of candidate vaccines and therapeutics.” Its Modular Immune In-Vitro Construct, MIMIC®, features an in vitro human immune system that enables researchers to test a human-like immune response to a vaccine or drug. This platform will be used to predict effectiveness, cross-protection capability, potency, as well as dosing and timing, of drugs and vaccines before costly clinical trials. MIMIC® technology can speed up evaluations of vaccines and vaccine stockpiles for safety and effectiveness before administering to the public.

Pfenex Inc. was awarded the last contract for up to a total of $18.8 million for “… innovative methods in bioprocess development and manufacturing.” With funding, the San Diego protein production company will continue to develop its recombinant protective antigen development program using the Pfenex Expression Technology Platform™ to identify protein expression strains that will produce stable high quantities of recombinant protective antigen (rPA) from anthrax. Applied technology will then be used to further develop bioproduction processes for a possible anthrax vaccine candidate.

Several recurring themes emerged in the presentations by the world’s experts in fields like public health, national security, food defense, biological weapons, and new advances in research.  Here is our analysis of some of the trends observed at the conference.

Narrowing the range of threats through risk assessment

Conference participants cited a wide variety of recent infectious disease outbreaks at the meeting; examples ranged from emerging infections like SARS and swine flu to endemic health threats like malaria and foot and mouth disease.  Further, no discussion of the topic would be complete without mention of the 2001 Anthrax bioterror attacks and the previous unsuccessful attempts by groups like Aum Shinriyko.

The point that all participants agreed on was that the biosecurity challenges of the future cannot be solved by purely brute force attempts to address every possible outcome.  Instead, the focus must be on more versatile measures that are better suited to addressing the unknown.  Risk assessment and improved surveillance play important roles in this effort, as these tools can be used to give as much advance warning of an outbreak as possible, so that other efforts can have the maximum possible time in which to respond to the threat.

The uncertain market for unknown treatments

Though there is controversy surrounding the exact cost of developing new treatments, most observers agree that the process can be both lengthy and expensive.  When the goal is to treat a condition that is already present in the population, such as cancer, HIV/AIDS, or malaria, a private company can determine the size of the potential market and secure funding based on that expected demand for the finished product.  By contrast, a company that is considering work on a vaccine against biological weapons is in the paradoxical position of hoping that their product will never be used, while still requiring some expectation of recouping their costs down the road.

Industry participants at the conference, from the smallest start-up to the largest pharmaceutical giant, were in unanimous agreement that the present lack of certainty is deterring participation in the biodefense field.  All called for increased guaranteed purchases – a more common practice in the defense contracting arena – and improved clarity in regulations and contract requirements.  Unfortunately, there are no easy answers to this issue in a tough economic climate where resources are increasingly limited.  Policymakers need to weigh the potential benefits of developing and maintaining the infrastructure that would be needed to produce biological countermeasures against other pressing and sometimes more immediate needs.

Diseases without borders

Past outbreaks have shown that, more than ever, infectious diseases do not respect the borders between states, nations, and continents.  Participants agreed that all efforts to combat diseases – whether naturally occurring or the result of the misuse of biology – need to be collaborative.  However, this type of cooperation, especially when it requires organizations and governments to spend money on efforts outside their normal constituencies, can be challenging to justify and implement.

At the same time, it does appear that improvements in communications technology will facilitate efforts to combat disease.  In particular, all eyes appear to be on the internet, in the hopes of anticipating the next outbreak with the assistance of online news and social networking.

Wrapping Up

Biosecurity is a broad subject area, and many topics could be the subject of an entire conference on their own.  In this context, the impressive slate of speakers at BIO 2010 did an excellent job in introducing these issues to an audience that might be less familiar with them, including industry in the dialogue on biosecurity.  However, many pressing questions still have yet to be resolved, and it is critical that this discussion go forward in the future.  We hope that BIO will continue to host these discussions at its 2011 meeting, which is slated to occur in Washington DC (which, as home to policy groups like FAS and most Federal agencies, would be an ideal location to draw even more participation next year).

Tim Hortons @ BIO Canada (Credit: Allen Dodson)

The 2010 Biosecurity convention concluded with a round table discussion of the dual use risks associated with novel technologies, such as synthetic biology and nanotechnology.

Our complete coverage of the convention here at the FAS Biosecurity blog can be found at:
http://fas.org/blog/bio/tag/bio2010

In the interest of full disclosure, the Biosecurity blog acknowledges the free Tim Horton’s coffee shop, imported by the BIO Canada pavilion on the exhibition floor; this generous caffeinated support has been instrumental in ensuring the quality of our coverage of the convention.

Without further ado, the summary of the final panel follows:

Panelists:

Harvey Rubin, MD – Session Chair
Director, University of Pennsylvania Institute for Strategic Threat Analysis and Response
University of Pennsylvania

Jesse Goodman, MPH
Director, Office of Science, FDA
U.S. Food and Drug Administration

Jack Newman
Senior Vice President for Research and Development
Amyris Biotechnologies, Inc

Kevin Jarrell, PhD
CEO
Modular Genetics, Inc.

Robert Friedman
Deputy Director
J. Craig Venter Institute

Gigi Gramwall
Senior Associate
UPMC Biosecurity Center

Nanotechnology

Dr. Rubin opened the discussion by raising the topic of nanotechnology.  He asked the panel how nanotechnology affects medicine, and whether there are safety concerns.

Director Goodman stated that FDA premarket review process would cover nanotechnology with the same criteria and regulatory pathways that cover other potential treatments.  However, as an emerging technology with toxicology characteristics are not yet fully understood, he stated that more data is needed to predict how nanoparticles will behave.

Dr. Friedman drew a distinction between biological agents and nanoparticles in that nanoparticles typically are not self-replicating.  This matters because the molecular threat is not expected to be amplified if released into the environment.

Do-It-Yourself (DIY) Bio

Dr. Gramwell tied nanotechnology in with synthetic biology and the rising “DIY Bio” movement, noting that the barrier to entry is comparatively low and, as with nanotechnology, regulations have not yet necessarily caught up.  Individuals who may not have training, experience, or a community capable of evaluating their work are increasingly in the position to engineer life.

Dr. Jarrell’s experience as a researcher dated back to the early days of recombinant DNA.  Based on this experience, he cited a need to balance innovation with safety.  His training taught him that modifying DNA is a privilege that should be exercised safely.

Dr. Newman referred to the various manipulation technology as “dual purpose” and called for risks to be weighed against the consequences of inaction.  For a disease like Malaria, with millions of potentially preventable deaths, he felt that the risks should be balanced against the potential benefits.  To stimulate the field, he recommended that individuals be empowered to participate in the building of the industry.  He caveated this suggestion by noting that the key question is whether allowing greater numbers of people to participate in the reprogramming of life is worth the risks.

Dr. Gramwell agreed that the DIY/garage biology movement evokes strong responses.  She suggested that these techniques can be put to a variety of beneficial uses, citing student projects that have uncovered incidents where stores and restaurants have served cheaper, low-quality fish while fraudulently claiming that they were offering more expensive options.

In reference to the dual use issue, Dr. Rubin cited the example of the reconstruction of the 1918 Influenza virus, which was published after lengthy deliberations.  In general, the community agreed with that decision, though it was not without its critics.

Dr. Friedman drew a distinction between DIY Bio conducted using non-hazardous microbes versus potentially dangerous pathogens.  New technology that facilitates DNA synthesis has the potential to lower the accessibility bar to these pathogens, but – for the moment – much of that DNA comes from commercial providers who are beginning to monitor for sequences of concern.

Dr. Gramwell noted that the creation of select agents is illegal, regardless of whether it is done in a DIY context.  However, she observed that the limits of these types of regulation extend only as far as our own borders.

Intellectual property

Dr. Friedman discussed the purpose of the patent system in spurring innovation for the public good in the context of patenting of living organisms.  He conceded that there is no clear consensus on how to address this issue yet.

Dr. Newman argued that the status quo for biotech patents will have to shift to a model that supports the combination of inventions towards a greater end.  He feels that attempts to commercialize living organisms can invite public backlash.

Director Goodman observed that socially we often fail to explicitly describe the positive and negative uses of a potential technological advance, and suggested that this exercise might help us weigh the pros and cons of these questions.

Unwise science?

Director Goodman raised the question of whether there are types of research that, regardless of the ethics and regulations, are unwise pursuits.  Would the people conducting such dual use research know it?

Dr Jarrell’s view of synthetic biology is that the focus of the discussion has been on its use to accomplish bad ends.  However, he defended the potential use of the technology to combat pathogens.   In one example, his company uses synthetic technology to try to produce renewable alternatives to existing chemicals that require the use of petroleum.

Dr. Friedman suggested that, while it may not be possible to remove all risks, it may be possible to address a large portion of the risks without losing the benefits of most legitimate research.

The current national security strategy ultimately focuses more on biologists becoming terrorists than on terrorists learning biology, and therefore places an emphasis on social institutions to encourage responsible culture within biology.  Dr. Rubin suggested the perhaps a code of conduct could potentially be effective in encouraging this responsibilities.

Dr. Gramwall agreed that codes of conduct are useful, but was skeptical of their ability to deter misuse.  Moreover, she worried that the techniques that are needed to carry out an attack may be more prevalent than people acknowledge.

Forbidden knowledge

Dr. Rubin raised the question of whether limitations on specific knowledge could help mitigate threat.  However, these types of measures impede the evaluation and reproducibility of science.

Gerald Epstein of AAAS argued that sequences that exist in nature as public health threats must be made public in order to combat threats that will exist regardless of regulations.

Director Goodman argued that there are topics that do not appear to be immediate risks but that a more determined malicious user could harness in unexpected ways.  However, he worries that companies underestimate the dangers and overestimate their own ability to mitigate them.  In a large enough aggregate, he fears that a failure somewhere in the system grows increasingly inevitable.

Dr Newman looked to all of the benefits of biotechnology, compared to the very limited number of incidents of misuse, and argued that education can further reduce the already improbable threat.

Larry Kerr from the US Office of the Director of National Intelligence argued that we have seen a significant increase in the education of policymakers to the concept that most biotechnology is potentially dual use.  However, this complicates risk assessment because the ambiguity of the threat can be concerning.  In Kerr’s view, individuals who are already intent on developing bioweapons capability may be beyond help, but he prefers to believe that junior researchers who are raised in a culture of responsibility can be influenced against harmful use of biology.  He notes that the national security community has not required censorship of publications, but observes that publications in these areas have proven responsible in the absence of any requirement.

Asked what industry can do to improve the perception of biotechnology, Dr. Rubin said that BIO has done a good job of communicating the benefits of the science.  However, Dr. Friedman argued that the community can help by demonstrating that scientists and companies have fully and thoroughly evaluated all of the potential risks.

Joe Kanabrocki – Chair
Assistant Dean for Biosafety, Biological Sciences Division
The University of Chicago

As a practicing biosafety professional with 20 years of experience, Dr. Kanabrocki argued that the role of a biosafety officer is to promote a culture of responsibility.  Biosafety has expanded from safeguarding labs to broader concerns about biosecurity and biosurety – ensuring the reliability of personnel.  With the expansion of facilities and the increase in security concerns, there have been increased calls for more oversight over biomedical research.

Michael Firko
Director, Select Agent Program, Animal and Plant Health Inspection Service
USDA

Director Firko, who oversees the programs for plant and animal pathogens, described the current procedures within the US Select Agent program.  The Select Agent program was created in 1996 and refined in 2001 and 2002.  The program authorizes CDC and USDA to regulate human, animal, and plant pathogens and toxins.    All researchers are subject to a security risk assessment administered by the FBI, designed to exclude individuals from working with dangerous pathogens if the candidate has concerning criminal or mental health history, or certain other risk factors defined by US law.

In addition to these requirements, biosafety lab procedures can impose specific requirements on the containment of pathogens, such as requiring a facility biosecurity plan on top of biosafety plans required to protect researchers from accidental exposure.  For example, the USDA BSL-3 requirements include personnel security levels for all employees within a facility, with increased scrutiny  of individuals with more access to pathogens.

Rob Weyant
Director, Select Agent Program
Centers for Disease Control and Prevention

Dr. Weyant is Dr. Firko’s counterpart at the CDC, and is responsible for overseeing human select agent pathogens.  He discussed the physical security requirements of the select agent program.  Facilities must have a security plan based on a site-specific risk assessment.  These assessments evaluate the agents present in a facility, along with ways that these agents are being used.  The security plan must address physical security to the building and labs, digital security surrounding information systems, and accurate inventory control of the stored pathogens.  The requirements also mandate the training of all employees in biosafety and security procedures and reporting of any incidents.

Details on these policies, and how to comply with them, are available at the National Select Agent Program website: http://www.selectagents.gov

John Nash
Chief Operating Officer, National Emerging Infectious Disease Laboratories
Boston University

Dr. Nash presented a hands-on view of how his facility, the new BSL-4 lab under construction at Boston University, has implemented the regulations in practice.  The facility is intended to permit cutting-edge investigator-initiated research on pathogens that cannot be studied in less secure facilities.  In addition to the federal regulations described by Drs. Firko and Weyant, the BU lab has to comply with Boston city public health regulations, and Nuclear Regulatory Commission requirements imposed on most biomedical research labs for the use of radioisotopes.

The biosecurity policy aims to protect against outsider threats from external individuals, insider threats from employees, and accidental threats from any containment breaches.  Suitability requirements for employees include criminal background checks, the FBI security risk assessment, financial background checks and medical clearances.  An additional policy covers visiting scientists, who must be supervised at all times, and must meet the same requirements for access to the facility as permanent employees (a process that Dr. Nash concedes is lengthy, but believes to be necessary).

Hamilton Mixon
Senior Director for Risk and Global Security
Vertex Pharmaceuticals, Inc.

Mixon offers the perspective of small to medium-sized companies that would like to work on select agents.  He praised communication tools, such as the select agent website, for helping to clarify requirements.  The need to comply with formal regulations helps corporate safety officers make the case to their corporations for the resources they need to ensure safety.

The two sides were in clear agreement on the need for more resources to address the potential for biological threats.  All present felt that agencies, such as the US Food and Drug Administration, require more funding and personnel in order to carry out their mission in a timely and effective manner.  All also agreed that the threat of new and unexpected pathogens is real and could be imminent.

The government side of the panel included Michael Kurilla (head of biodefense programs at the National Institutes of Allergy and Infectious Disease within NIH), Nicole Lurie (the Assistant Secretary for Preparedness and Response at the US Department of Health and Human services, and a speaker at the morning session), and James Gilman, commander of the Army Medical Research and Materiel Command.  This group emphasized the need for flexible and efficient responses that could be quickly directed to a variety of unknown and emerging threats.

The industry side of the panel consisted of Eric Richman, interim CEO of PharmAthene, Paul Chaplin, Executive VP for Research and Development and CSO at Bavarian Nordic, John Grabenstein, Senior Medical Director for adult vaccines at Merck, and James Davis, Senior Vice President at Human Genome Sciences.  This group emphasized the need for predictable markets for countermeasures in order to make the case to investors that biodefense projects are worth supporting.

The comparison was drawn to traditional defense contractors, who can sink money into developing a project secure in the knowledge that the DOD will ultimately purchase a certain amount of the completed project, should it be successful.  By contrast, a vaccine manufacturer might be expected to build an expensive dedicated facility, which would typically only be used for a single specific vaccine due to fears of contamination.  Without knowing how much to expect in sales revenue, the company can be hard pressed to determine how much it can afford to spend on partnerships and expenses in developing a project.

In the end, the solutions to administrative problems may need to be as creative as the solutions to scientific ones.  For instance, Admiral Lurie suggested that many potential bioweapons qualify for expedited review as “orphan drugs”, and also described a “speed-dating” like approach to fostering partnerships between companies that had a potential vaccine candidate and manufacturers capable of bringing that product to market.

AAAS Logo (Credit: http://aaas.org)

Participants at a January 11^th forum on Minimizing the Risks of Synthetic DNA, held at the AAAS, appeared to be in general agreement on the principles behind proposed US guidelines to safeguard the rapidly advancing technology of gene synthesis.

Synthetic biology, a new field made possible by developments in genome sequencing and genetic engineering, seeks to take an engineering-based approach to biological problems.  The story of the malaria drug Artemisinin provides an example of the advances that this new approach can produce.  The drug is currently made from a plant extract, and crop quantities are insufficient to meet global demand.  Through synthetic biology, scientists have been able to engineer yeast capable of performing the multiple reactions necessary to create the drug’s precursor.

However, engineering life also presents the opportunity to create existing, augmented, and/or novel pathogens.  Current restrictions on select agent pathogens, such as Smallpox, are based on the physical safeguarding of live bacterial and viral stocks to keep them from malicious users.  With modern gene synthesis technology, a would-be attacker could potentially obtain a complete pathogen genome by ordering it from commercial DNA providers.

It is in this context that Monday’s forum brought together a wide variety of stakeholders, ranging from Federal regulators to major gene synthesis firms and research organizations.  Though the specifics of guideline implementation were occasionally questioned, there was a surprising degree of consensus concerning future policies implemented by private industry.

Building Self-Policing Standards

The US Federal Government’s National Science Advisory Board for Biosecurity (NSABB) first weighed in on the gene synthesis issue in a December 2006 report, recommending in part that:

“…establishing uniform and standardized screening practices among providers of synthetic DNA would help safeguard against the intentional or unintentional circumvention of the [Select Agent Regulations].”

As the US government worked to clarify policies on this technology, synthetic DNA providers began similar efforts.  The fruits of these separate efforts were finally revealed in November 2009.

On November 3rd, the International Association Synthetic Biology (IASB), a group that includes biotechnology and gene synthesis companies in the US, Germany, and China, announced that it had completed its year-long effort to draft a code of conduct covering “ethics, biosafety and biosecurity aspects of gene synthesis.”  Shortly thereafter, on November 18^th, five major gene synthesis companies – Blue Heron, DNA 2.0, Genart, Genscript, and IDT – announced that they were forming the International Gene Synthesis Consortium (IGSC).  This group, which claims to represent 80% of the world’s gene synthesis capacity, issued a similar screening pledge.

Finally, on November 27^th, the US Department of Health and Human Services (HHS) issued the draft guidelines titled “Screening Framework Guidance for Synthetic Double-Stranded DNA Providers”.   The guidelines, which are open for public comment through January 26^th, were the subject of the AAAS forum.

The Proposed Standards

All three proposals are in broad agreement as to the basic procedures needed to prevent malicious double-stranded DNA orders.  Potential customers would be screened to verify their identities as legitimate researchers, while the ordered sequences would be examined to assess their similarity to pathogen genes.  In the event of red flags in either area, companies would further investigate orders to ensure that malicious individuals do not obtain potentially dangerous materials.  Representatives from industry groups did not feel that these procedures would add substantial costs to order processing or delays in shipping the final product.

Technical details of the policy will require further evaluation.  Researchers expressed concern that start-up companies without the support of an established research institution might have trouble demonstrating their legitimacy, which would now be required in order to request pathogen-related sequences.  Some scientists and providers questioned the validity and arbitrariness of a proposed 200 base-pair threshold for screening scrutiny, which was intended to exclude smaller, single-stranded oligonucleotides from safety proposals aimed at synthesis of full-length genes.

The question of which method should be used to determine the sequence origin – either the so-called “best match” model, which utilizes databases such as GenBank, or other sequence matching algorithms – was also a hot topic of discussion.  Indeed, some participants felt that this issue showcased an advantage of the voluntary nature of the proposed non-binding Federal guidelines.  The intentionally flexible language would allow the policy specifics, such as the matching algorithm, to evolve in the face of technological advances that move far faster than either formal rule making or legislation.

This voluntary approach may also facilitate global cooperation within the rapidly expanding international gene synthesis industry.  One DNA provider explained that their company would generally apply the most stringent standards mandated anywhere in the world they do business, rather than attempting to apply differing standards to individual orders depending on local regulations.

Ongoing Developments

The US guidelines for synthetic double-stranded DNA providers will be open for comment through January 26^th, and will be revised and reissued in final form later this year.  The NSABB is also continuing to investigate the promises and perils of synthetic biology; the board approved a new draft report in December 2009 calling for increased oversight, education and outreach concerning the dual use potential of synthetic biology.

Even as the details continue to be discussed, it is encouraging to see nigh universal consensus on the measures to safeguard the public from harm, while preserving the potential for societal advances presented by this growing field.

Highly infectious diseases are currently designated as select agents and regulated by the Departments of Agriculture (diseases of plants and livestock) or Health and Human Services (human pathogens).  The new legislation would replace this single list with three “tiers”, and research using the most dangerous agents would be overseen by the Department of Homeland Security.  An amendment by Senator Claire McCaskill would allow DHS to shut down labs that do not comply with safety regulations.  However, the bill would also implement so-called personnel reliability programs, common in nuclear research, as a condition for researchers to access the labs.  Recent reports by the government’s National Science Advisory Board for Biosecurity and the National Academies’ Board of Life Sciences did not recommend such measures at this time.

Though Lieberman, who chairs the committee, has made the bill a top priority, it is unclear when time would permit consideration of the legislation on the Senate floor.

Science reports that “officials found that lab managers ignored information about certain employees that could have disqualified them from having access to dangerous pathogens. The redacted version of the IG’s [Inspector General's] report released to Science does not divulge the nature of this so-called potentially disqualifying information, but it could be anything from alcoholism to mental instability.”

On October 28, 2008 AR 50-1 came into effect, stipulating a strict Biological Personnel Reliability Program for DOD employees as part of their Biological Surety Program. It includes and intense background investigation and interviews  of employees as well as regulations regarding substance abuse and mental health.

In early February the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) also suspended its research on biological select agents and toxins when it was realized that there were problems with the system of accounting for high risk microbes and biological materials in the laboratories at Fort Detrick, MD.