Definitions

Legal institutions in Germany, the European Union and the United States of America define the term dual use as the risk that chemicals, organisms or technologies can be misused for military purposes. This definition originates from the bioweapon convention in 1972. A point of view more adapted to recent developments in technology and the uprising discussion about research with biosecurity concern can be found in discussions and proposals of non governmental institutions and advisory boards, such as the World Health Organization (WHO), the National Science Advisory Board for Biosecurity (NSABB) and the Deutsche Forschungsgesellschaft/Leopoldina (German Academy of Sciences). Some define dual use to the potential of research results to be used in benevolent and malevolent purposes as well. As a result of our analysis, we find the definitions to vary between the different states and organizations. While organizations within the USA use the term for research results as described, in Germany this dilemma is referred to as “research with security concern”. This topic was addressed by Terry Johnson at a Giant Jamboree in Boston . Nevertheless, we could not find a definition of dual use within the iGEM safety page. More surprisingly, we did not find definitions of biosafety and biosecurity either. To promote a better understanding of the underlying principles and raise the awareness of the dual use dilemma, we want to provide definitions of biosafety, biosecurity of dual use and dual use research of concern.

Biosafety

"Biosafety describes the containment principles, technologies and practices that are implemented to prevent the unintentional exposure to pathogens and toxins, or their accidental release.” (World Health Organization, 2004)

Biosecurity

"Laboratory biosecurity describes the protection, control and accountability for valuable biological materials (…) within laboratories, in order to prevent their unauthorized access, loss, theft, misuse, diversion or intentional release."(World Health Organization, 2004)

Dual Use

The potential of knowledge to be used in both benevolent and malevolent ways is defined as dual use risk. In addition, the potential of items to be used for military purposes is reffered to as dual use potential. Research providing knowledge containing dual use risk is called Dual Use Research of Concern (DURC).

Dual Use Research of Concern (DURC)

The National Science advisory board refers the “generation and communication of information and new technologies from life sciences research that have the potential for both benevolent and malevolent application (…) along with the subset of dual use research with significant potential for generating information that could be misused (…) to as “dual use research of concern.” (NSABB, 2007)

In view of these non consistent definitions in such an important field, we see the necessity of an international definition to establish a uniform basis for discussion and establishment of guidelines. Containing both definitions, namely the potential use of goods or technologies for military purposes as well as the potential misuse of information and knowledge, we find the definition of the WHO to fulfill those needs. We consider biosecurity to be not only the protection of material, but also the prevention of risks that arise by the knowledge provided in research.

Laws

In our analysis, we find the legal situation in the European Union (European Union,2014), Germany (Federal Republic of Germany, 2012) and the USA (U.S. Government, 2015) to be inconsistent. Most laws only apply to the dual use items, such as chemicals. In some countries publications are dealt with as such dual use items and laws are applied, in others not. This inconsistency lead to a broad ethical debate.

Since it seems to be unclear, whether the existing laws apply, we see a definite need for an international regulation and a guideline. Such are proposed by various advisory boards, non governmental organizations and ethical committees. We further describe the laws in detail, possible guidelines, implications and proposals of those boards and committees and display various opinions in the broad field of ethical questions concerning dual use in our report.

Ethical questions

The discussion about moral and ethical questions of the dual use matter is of very broad range. The complete understanding of the ethical basis is far beyond the size of this record and requires a deep understanding of ethics. To display various points of view beyond the laboratory work and to complete our findings we contacted several experts and display a summary of different points of view.

Freedom and responsibility in science

The advances of communication technology create free access and communication. This is promoting the progress of science. Simultaneously, this freedom creates the possibility of access of this information for potential misuse (DFG/Leopoldina, 2010). Freedom of science and the possible need for restriction of information for security purposes are hence controversial and need to be weighed carefully.

Self regulation vs. institutional oversight

A self regulation process needs responsible participation of everyone involved in the path of research and its publication: researchers, funding institutions, cooperators, coworkers, editors and reviewers of journals, ethics councils and legal institutions. While this responsibility is called for by various advisory boards and non governmental institutions (European Commission, 2014, NSABB, 2007), the need for institutional oversight is still stated. Different points of view from experts are discussed in detail in our report. Among them is the point of view of Constantin Teetzmann, constitutional lawyer. He promotesa self regulation process involving expert advisory. Prof. Kathryn Nixdorff points out the importance of oversight and education. Prof. Alfons Bora explains the idea of reaching out to everyone conducting research and education. In addition, several advisory boards promote institutional oversight and international regulation.

Responsibility of publishing institutions

Editors are the ones making final decisions about the publication of research result. They collaborate with reviewers in the process of publication. Therefore those persons in charge should be guided by further educational courses on dual use issues and the incorporation of their needs in biosecurity guidelines. Nevertheless, this establishment can only be a part of the progress of responsible oversight.

“To try to prevent misuse at the publication level serves no purpose, this is too late. By then, detailed knowledge about the contents of the publication is already known to collaborators, and the work has in most cases been presented at meetings. (…) The point of oversight and application of mitigating measures must begin at the planning stage and continue throughout the experimentation process until the work has been completed. This is why the risk assessment your Bielefeld-Team proposes is so important. Identify risks at the very beginning and find ways to mitigate those risks before any risk-laden methods become public knowledge.”

Prof. em. Kathryn Nixdorff (Department of Microbiology and Genetics, Darmstadt University of Technology)

Responsibility of the researchers

Because up to now no legal restrictions apply, the researcher himself is making the decision in collaboration with ethic councils, whether the benefits of the research outweigh the risks, whether there are ethical or moral reasons not to investigate the question of concern and whether the results can be (partly) published. The decision is made at the planning stage. This moral reasons need to consider the consequences of science – such as application in pharmacy, medicine and other fields (DFG/Leopoldina, 2014).

Conclusions

While we were unable to include a deep ethical analysis in a report of this size, the summary of ethical questions points out the necessity for the implementation of the dual use issue in research at the very beginning. The education and advisory of young researchers is a key step towards this goal. Only if the awareness of the dual use issue is implemented in education, researachers can participate in an ethical discussion. To ensure these progresses, advisory institutions, such as ethical commissions, need to be established. While the optimal solution would be international applicable guidelines, which advisory boards are reaching out for, we believe iGEM to have the unique chance to be a role model in international collaboration and education of young researchers.

Biosafety and Biosecurity in iGEM

Every team is dealing with genetically modified organisms, methods of synthetic biology to analyze, combine and build those organisms and DNA parts, respectively. Therefore, the question of regulation is given in context of biosecurity and biosafety. It needs to be dealt with within each team and the competition itself as well.

Biosafety and Biosecurity in iGEM

However, we could not find definitions of biosafety, biosecurity, dual use and dual use research of concern (DURC) within the iGEM safety page. In terms of biosafety, obligational forms need to be filled and check-ins for certain organisms and proteins are required. A list of organizations publishing instructions and legal regulations for different countries is provided, since iGEM faces the challenge of teams from a broad range of countries. Regarding biosecurity on the other hand, we found questions to be asked in context of safe project design, such as “To whom will it be benefitial or harmful?” on the safety page. It is noticeable, that the questions asked try to cover a mixture of biosafety and biosecurity issues. The answers differ among the iGEM teams in a very broad spectrum. Interestingly, the questions aim to the designed product or the used methods/chassi. The information that are distributed among our society by the team´s homepages, wiki and other published materials is not addressed. In our view, the question concerning security in the safety form aim for the product rather than the knowledge too: “What risks might your project pose, if it were fully developed into a real product that real people could use? What future work might you do to reduce those risks?” We think that biosecurity risks need to be defined and the question to be asked more precisely.

Dual Use Dilemma in iGEM

Nevertheless, iGEM members are supposed to live up to the trust that is put into them by society and “design, build and share biological devices safely” (iGEM Safety Page). Aspects of dual use have found focus in Terry Johnson´s call for awareness: iGEM participants, but also participants anywhere in the biotechnological environment, “should be aware of: the organization or organizations overseeing (ones) work, the appropriate Risk Group for the organisms that (one is) working with, and any select agents that might be involved. Further consider: any potentials for dual use, and especially if there are any biosafety or biosecurity concerns that are not addressed by current administrative controls”. (Terry Johnson, 2013). Interestingly, the security page of 2011 contains details about biosecurity risk assessment. The possible misuse of information is pointed out. At the time of this year's project design and conduction neither on the main iGEM page nor on the 2015 page a security page was existent. Nevertheless, the iGEM competition established a safety committee that has members with very deep knowledge about the dual use concern.

Conclusions

Facing this dilemma in our own project, we have not found proper guidelines within the competitions to apply to our concerns. While iGEM provides expert council through its safety committee, we find this not to be sufficient to call for awareness of dual use in all states of research. As proposed in our description of the ethical debate, this is critical for the planning of research. Therefore, we propose the implementation of biosecurity risk assessment in obligational forms. Since the iGEM competition asks us to be “striving to be conscientious members of the synthetic biology community” (iGEM Safety Page), we want to complete this safety and security aspects by finding guidelines for the safe distribution of knowledge and the question of dual use research of concern. As it is an international competition aiming to promote the communication between researchers as well as between them and the public, iGEM could be a role model in considering the dual use dilemma.

Proposals for the iGEM community

We propose the implementation of the definitions of biosafety, biosecurity and dual use in the iGEM safety page. This is suggested to increase awareness of biosecurity risks and especially the dual use issue from the very beginning of research progress in iGEM projects.

Further, on advice of Prof. Nixdorff and in hindsight of the proposals of several advisory boards, we propose a general biosecurity risk assessment by implementation of additional questions into obligatory safety forms. This assessment cannot be strictly seperated from biosafety questions, as the security measures need to be adapted to the biosafety risks:

General biosecurity risk assessment

• Do you work with any sequences or toxins of plant/animal origin, that might be a threat to health of humanity or environment?
• Do you work with any sequences of S3 organisms or does your work contain any sequences or proteins specifically produced/contained in these organisms?
• Do you provide any knowledge of constructing, manipulating or influencing these agents or toxins?
• Do your experiments meet any of these criteria or provide knowledge about the conduction of these experiments?
  1. “Enhances the harmful consequences of the agent or toxin
  2. Disrupts immunity or the effectiveness of an immunization against the agent or toxin without clinical or agricultural justification
  3. Confers to the agent or toxin resistance to clinically or agriculturally useful prophylactic or therapeutic interventions against that agent or toxin or facilitates their ability to evade detection methodologies
  4. Increases the stability, transmissibility, or the ability to disseminate the agent or toxin
  5. Alters the host range or tropism of the agent or toxin
  6. Enhances the susceptibility of a host population to the agent or toxin
  7. Generates or reconstitutes an eradicated or extinct agent or toxin listed above”

  (United States Government, 2015)

• Who has access to your laboratory?
• Do the persons with access to the laboratory receive prior training?
• Did you apply additional biosecurity measures to any used substances? Describe the measures.

Dual use risk assessment

• Can you imagine any malevolent use of the knowledge and sequences published on your team’s wiki? Could the knowledge you provide be in direct consequence used for the creation of products or organisms that pose a danger to humans or the environment?
• In case of collaboration, does the sharing of devices or information create the potential of misuse?
• In case of potential risk, did you initiate oversight or seek ethical/legal council or advice?
• How where your concerns addressed in your project?

Prospect

We favor the implementation of international applicable guidelines for biosecurity and dual use risk assessment. We found the importance of the establishment of oversight and assessment in every state of research progress, beginning at raising awareness of the risk up to the establishment of the risk assessment in hindsight of research: publication and collaboration. The detailed implementation and process is displayed in our report.

Integration in our project

The dual use dilemma was first discussed, when our team was looking for information about a date rape drugs, since we aimed to develop a biosensor detecting ingredients in these drugs. We were astonished, how many, in our eyes, sensitive information we found free for access on the internet. These information contained detailed instructions of availability of chemicals on the free market that could be used as date rape drugs, as well as instructions of synthesis of these drugs. We were wondering, why these information are freely available and if there are any laws applying publication of sensitive information.

Laws

Our project is aiming to build a biosensor for detecting ingredients of date rape drugs with the prospect of enabling people to protect themselves. Nevertheless, we focus attention on these ingredients and their availability and hence provide knowledge that might be misused to harm people. Therefore we analyzed the legal restriction of the providence of this knowledge not only in our country (Germany), but also in the European Union as confederal institution and in the USA, where iGEM takes place. We did not find laws applying to the publication of this knowledge, which is therefore legally justifiable.

Ethics

While providing this knowledge might lead to misuse, it has benevolent content. By publishing our obtained knowledge, we might inspire others to improve a sensor for the protection against date rape drugs, but also to build other biosensors detecting harmful substances in beverages in hindsight to our aim to provide a modular, extensible tool for the further creation of biosensors. In addition, our knowledge might raise the awareness of availability of the used chemicals in date rape drugs. This could ultimately lead to a more careful handling of beverages or even the overthought of legal obtainability and restriction of these chemicals, as we caused a broad discussion in the media. These findings lead to our ethical analysis in collaboration with experts from microbiology, law, sociology and ethics. Do the potential benefits of the publication of our results outweigh the potential risk? Since we are not providing knowledge how to synthesize or obtain these drugs, we still focus attention on these substances. Therefore, we decided to apply security risk assessment to our project.

Risk assessment

The process of risk assessment as proposed by our team is conducted at every stage of our research. We do not aim for restriction or prohibition of research or progress, but for raising awareness and thereby minimizing the risk of misuse in a process of free and responsible science.

• Awareness

We raised awareness in our team and collaborating coworkers within our institution of the potential danger of the misuse of our knowledge and inspired a discussion about the issue.

• Training and education

While up to this point in our curriculum and education the dual use issue was not yet addressed, we educated ourselves about the dual use issue by a detailed analysis in our report and fruitful internal team and external discussions with experts on this topic. We further initiated a discussion about the importance of the issue with our team advisors and instructor. This discussion can initiate the education of following teams. We propose the implementation of definitions and risk assessments in the iGEM safety page to improve the awareness and education of future generations of iGEM teams.

• Safe experimental design

While the ingredient is legally available without restrictions in Germany, we still handled it as potentially dangerous substance. We deposited it in a locked poison storage with limited access. Documentation of the usage of the substance was initiated. All participating coworkers were informed about the potential risk of the substance. We discussed the handling with our team advisors and supervisor.

• Regular oversight

In our weekly team meeting the upcoming publication of the substance and details about our sensor were discussed in hindsight to potential dual use risk. Experts were contacted, such as the ethics committee at our university, the iGEM safety committee itself and of course our supervisor. Regular oversight by an institution is not yet established.

• Minimizing potential risk

We found restriction of publication in this case not to be effective to minimize the risk, since we do not provide the knowledge of how to obtain or synthesize the ingredients of the date rape drugs. Said information are obtainable astonishingly easily, therefore our call for awareness and providence of knowledge to create a biosensor contains more benevolent content than potential risk.

• Documentation and communicationWe documented not only the use of the chemical, but also our concerns about biosecurity issues. We contacted the ethics council of our university that unfortunately is not yet established for biotechnological research. The interview is available in our report. We further contacted the iGEM safety committee for advice on publication. Mrs. Kelly Drinkwater, member of the iGEM safety committee, agreed on our proposed publication.

  “I looked up GHB and GBL on Wikipedia and it's very easy to find information about these two molecules, including the fact that one is a precursor of the other, and even some scientific references about how to synthesize them. Because this level of detail is freely available, I don't think the documentation of your project has any risk of facilitating the misuse of GHB for harmful ends. The level of detail you provide about these molecules is entirely appropriate. (Of course, you might have some commentary about the legal status of GBL compared to that of GHB. As you point out, it is a little odd that GHB is regulated so much more strongly than its precursor molecule.)”

  Kelly Drinkwater, iGEM Safety Committee

• Publication

We decided to publish our knowledge on our wiki in full size to enable the construction of a biosensor to protect oneself. We did not restrict or delayed publication, because we found the critical knowledge about how to obtain or synthesize the date rape drugs already published by several easily assessable webpages.

Answers to proposed questions for biosecurity risk assessment implementation

General biosecurity risk assessment:

• Do you work with any sequences or toxins of plant/animal origin, that might be a threat to health of humanity or environment?

→ No.

• Do you work with any S3/4 organism’s sequences or toxins or does your work contain any sequences or proteins specifically produced/contained in these organisms?

→ No.

• Do you provide any knowledge of constructing, manipulating or influencing these agents or toxins?

→ No.

• Do your experiments meet any of these criteria or provide knowledge about the conduction of these experiments? If yes, which?
  1. “Enhances the harmful consequences of the agent or toxin
  2. Disrupts immunity or the effectiveness of an immunization against the agent or toxin without clinical or agricultural justification
  3. Confers to the agent or toxin resistance to clinically or agriculturally useful prophylactic or therapeutic interventions against that agent or toxin or facilitates their ability to evade detection methodologies
  4. Increases the stability, transmissibility, or the ability to disseminate the agent or toxin
  5. Alters the host range or tropism of the agent or toxin
  6. Enhances the susceptibility of a host population to the agent or toxin
  7. Generates or reconstitutes an eradicated or extinct agent or toxin listed above”

→ No.

• Who has access to your laboratory?

→ We work in a biosecurity level 1 laboratory. The building and each laboratory section is secured by electonical devices limiting the access. Public access is not possible. Members of the working group have access.

• Do the persons with access to the laboratory receive prior training?

→ Yes. Every person with access receives prior training following the rules for S1 laboratory safety instructions.

• Did you apply additional biosecurity measures to any used substances? Describe the measures.

→ Yes. We stored GBL, the substance of possible biosecurity concern, in a locked poison storage with limited access and, as described before, documented the usage of the substance.

Dual use risk assessment

• Can you imagine any malevolent use of the knowledge and sequences published on your team’s wiki? Could the knowledge you provide in direct consequence be used for the creation of products or organisms that pose a danger to humans or the environment?

→ Yes. We focus on the availability of an ingredient of date rape drugs. This potential misused has been evaluated carefully. The benefit of the published knowledge outweighs the potential risk, because we found the critical information already published and easily assessable. Therefore, our knowledge provides protection by creation of a biosensor and raise of the awareness of the potential danger of date rape drugs.

• In case of collaboration, does the sharing of devices or information create the potential of misuse?

→ Sharing the device does not contain the risk of misuse. Sharing the information contains the same risk as publication of said knowledge.

• In case of potential risk, did you initiate oversight or seek ethical/legal council or advice?

→ Yes. We contacted the ethics commission of our university and the iGEM safety committee. Unfortunately, no advice could be given by our ethics commission. The iGEM safety committee agreed with us, that the information we provide is already published and easily accessible and therefore does not contain a risk that would justify the restriction of publication on our wiki.

• How were your concerns addressed in your project?

→We addressed the dual use issue and biosecurity concerns in a detailed analysis as proposed here. We propose the integration of biosecurity measures for further teams. We educated ourselves about the laws and regulations. We discussed the concern with our advisors and instructor. We decided to conctact the ethics council at our university and the iGEM ethics committee. We applied additional biosecurity measures to the substance of possible biosecurity concern.

Interviews

For our report about Dual Use we worked with various experts in ethics, laws and sociology. The complete interviews and statements are available in the report itself.

Prof. Kathryn Nixdorff (Microbiology)

The report (“Dual Use - A report by the Team iGEM Bielefeld-CeBiTec 2015”) the Team iGEM Bielefeld CeBiTec 2015 has submitted in the context of the iGEM competition, as an aspect of their synthetic biology project, is in my view an innovative contribution that will help promote the aim of the iGEM to foster conscientious members of the synthetic biology community. Several surveys over the past ten years have clearly documented that the majority of scientists involved in modern life sciences work do not devote a great deal of active consideration to questions of biosecurity, mainly because they have little awareness of possible dual-use implications of their work. In the iGEM competitions, a lot of emphasis is placed on working safely, with required questionnaires, which, however, mainly cover biosafety aspects of their work. This is an excellent procedure and imperative to working responsibly. While the efforts of the iGEM organizers to promote awareness of biosecurity issues are growing steadily, the same rigorous questioning about dual-use biosecurity risks in carrying out the iGEM projects has to my knowledge not yet been applied. The proposal of the Bielefeld-Team to assess possible dual-use biosecurity risks in the context of all iGEM competition projects is a step in the right direction to promote awareness of biosecurity concerns among competition teams and to allow them to demonstrate that they are acting responsibly not only with biosafety concerns, but also with those related to biosecurity. I consider this relevant and necessary in light of the steadily growing reports of work involving dual-use research of concern (DURC) in the scientific literature that have generated much controversy and debate in the scientific community and in the general public about the need for carrying out research in a responsible manner. In my opinion, the proposal of the Bielefeld CeBiTec Team is a needed step that can definitively complement the standing efforts of the iGEM organizers to foster conscientious members of the synthetic biology community."

Professor Alfons Bora (Sociology)

"The aspect of dual use deserves highest attention, both in science and politics. Therefore, national states as well as international organisations are obliged to monitor all relevant trends and to apply regulation, where necessary. Equally important, however, is the responsibility of scientists and their organisations. The training of young scholars, the implementation of clear and expedient rules and monitoring mechanisms, and the obligation to take dual use aspects into consideration at any step of the research process are important components of scientific self-regulation."

Constantin Teetzmann (Constitutional Lawyer)

"The iGEM competition could strengthen responsible decisions on the dual use research while respecting freedom of research if it provided the necessary resources. The competition offers already one resource by its very nature: iGEM is a good forum to discuss the issue. The second one needs to be developed: well-founded decisions about dual-use research need factual knowledge and normative considerations. Information about the facts and different normative perspectives on the problem could be published within iGEM and institutional points of contact might be established. It would be great if such point of contact could provide counseling and help to examine the issue on all relevant aspects. The decision would still stay with the team and ultimately with every individual researcher. Therefore, any advice shall not get judgmental or take over the decision by giving specific recommendations."

Joseph Ayar (J.D. candidate, Santa Clara School of Law)

"Different perspectives within iGEM, such as legal and ethical, not only help to ground scientific research within the current legal and ethical framework, they can even help drive the progression and evolution of the framework itself. Bielefeld-CeBiTec’s report on dual use research is a manifestation of such a collaboration as it provides the building blocks for a responsible approach to a field that is advancing at an ever-increasing pace."

Additional interviews

To analyse the current situation at our university, we further contacted and interviewed Prof. Bohner, head of the ethics commission of our university. He is professor in the department of psychology and provided us valuable insights on the current status and possible further implementation of council for researchers at our university. The analysis of applicable laws and responsibilities of the german legislation are complemented by an interview with the German Federal Office for Consumer Protection and Food Safety, Department 4: Genetic Engineering.