I am biochemist by training. I worked several years in several basic research labs, my last place was the Institute for Medical Microbiology, Virology and Hygiene at the University Medical Hospital Centre Eppendorf here in Hamburg. Currently, I am working at the Centre for Science and Peace Research at the University Hamburg and I am specialized in biological arms control and biosecurity matters. Besides that, I am working at the Department for Microbiology and Biotechnology on projects involving bacteria such as Bacillus thuringiensis as well as the pathogenic bacterium burkholderia.

Synthetic biology aims at the introduction of new, engineered biological synthesis pathways by the use of very selective, focused genetic engineering. One work horse would be the use of genetically modified organisms (GMO) which will show the novel, artificially introduced elements, called sometimes “BioBricks”. That are (at least in theory) fully understood, well described biologically active elements such as expression genes, selection makers or controllable promoters which allow induced gene expression for example. Synthetic biology thrives at taking full control of biological process for the good. Examples would be the production of otherwise inaccessible chemical substances such as complex organic molecules essential curing diseases.

But if you start working with biological material/biological agents, very soon you want to be sure that all work is done in a safe manner. Nobody wants to get an infection by bacteria or viruses used in the genetic engineering lab. Therefore, a set of rules and ordinances have been developed over the last decades which support scientists and co-workers to perform their experiments in a safe way. Biosafety regulations and biosafety measures help us in our daily work and every employee (and even lab guest!) have to be introduced to them BEFORE entering the lab and start the work.

But there is also another side of doing work with biological agents, especially, if there are pathogenic or can cause an intoxication. Other people, seeking to cause harm by using biological material, can use make use of our agents you are working with or the knowledge you obtained or even the equipment you are using. Who would that be? Think of bioterrorists for example who want to spread terror using disease-causing biological agents. But theft might also be a problem. “Biocrime” is a term which refers to the misuse of biological stuff to cause harm or kill people on the level of an individual perpetuating individual criminal goals. Or think of states interested in the development of weapons of mass destruction (WMD). That could be nuclear weapons, chemical weapons or … biological weapons! That had happened in the past already! So, we know from history, that state-driven biological warfare programs potentially could reach a high level of sophistication. The Biological and Toxin Weapons Convention (BWC in short) was put into force in 1975 and prohibits the development, production, stockpiling etc. of biological and toxin weapons (BW) and requested member states to completely destroy potentially existing BW stockpiles as well as the destruction/conversion of development, production, storage and testing facilities used for offensive purposes. So, also in Germany being one of the 178 members of the BWC the development of biological weapons is forbidden by national law! But in the past, there were also illicit offensive BW activities, e.g. in the former Soviet Union or in Iraq. In this respect, also some kind of knowledge transfer took place during the Cold War allegedly involving also Egypt, Syria, North Korea, China or Iran. No hard proofs there in the public domain so far as I know. But from the lessons learned about the Iraqi BW program, more and more non-proliferation activities were put in place which aim at the mitigation of any transfer (proliferation) of materials, technologies, equipment as well as knowledge usable for the development of WMD. One example is UN Security Council Resolution 1540 issued in 2004 calling all UN member states to implement appropriate proliferation counter-measures.

Today, we term measure aiming at the mitigation of misuse of biological material and scientific knowledge as biosecurity measures. Biosecurity is not thought to impair science, but to allow scientific work taking place in safe and secure working environment! And there is some good news: many prerequisites for a robust biosecurity regime are already covered by biosafety measures anyway in place - if these measures are comprehensively implemented and obeyed.

And how you can help us setting up required biosafety and biosecurity measures?

Most importantly, you have to learn about the German legislation dealing with biosafety (“Biostoff-Verordnung”, “Gentechniksicherheitsverordnung”,” Technische Regeln für Biologische Arbeitsstoffe”, „Infektionsschutzgesetz” and so on). But I learned know from you that you already are in the picture. You seem to be in touch with all the right people at the university, who are responsible for giving you advice and who should supervise the work you are planning to do. Biosafety measures are important to protect yourself, your coworkers and the environment from biological hazards. One important pillar is to conduct the mandatory risk assessments BEFORE you start your work. It is of great importance getting all required official licenses by the local authorities in advance. Usually, you will get great support by the authorities in the planning phase, because they want to support progression of science.

The rules of the iGEM competition demand from any project team the awareness and the will to think about safety AND security implications of the planned work and … very importantly of the “products” of your work. One cannot ignore the responsibility of all of your iGEM team members for the experiments and the results! You have to take the responsibility and do everything you can in order to (a) set up a really fancy iGEM project … but on the same moment (b) do a proper risk assessment and do everything to minimize potential misuse of your work. The latter might ring a bell: it is the biosecurity aspect of your work I am speaking about now.

Therefore, you have to know about the (many, many) good things, but also about the bad things about science. In my talk, I presented to you the historical context of biological warfare, the misuse of biology which once happened to fulfill hostile purposes. And there might be still nowadays actors who are very interested in the knowledge and products you obtained. Therefore, you have to restrict access to your lab space, you have to restrict access to your lab journals and technical background papers, and you should not spread knowledge about your project in great details. Especially, when you use information channels where you do not have control about the flow of information.

There are technical barriers which you can implement in your project in order to prevent misuse. The iGEM rules give you an orientation here, what would be important to think about (one key word here: genes encoding toxins. Are you allowed to work with them? Is it really necessary to work with them? Can you assure that nobody would make hostile use of them once you finished your project?). We already discussed your project plans and found some promising ways to implement effective safety and security barriers. That is, because on the one hand your project is challenging and involves design concepts showing a certain dual use potential, on the other hand there are experimental steps which easily allow the integration of certain, well accepted security barriers.

To sum that up: Ideally, biosecurity measures are founded on the basis of appropriate biosafety measures and encompass both additional theoretical and practical steps to prevent the misuse of biology. You did already the right steps to implement biosafety as well as biosecurity measures. Our discussion about details of your project resulted in a well-balanced biosecurity concept.

What is dual use research of concern? How does it affect our plans?

The term “dual use” means, that you can use s.th. – in our case scientific achievements - for the good, but also for the bad. We already touched the topic “misuse of science for hostile purposes” several times now. To make it clear again: Many aspects of biological sciences show a dual use potential: biological materials you are working with, equipment and technical information you use, knowledge you use or produce by yourselves. But there is a category of research endeavors which go far beyond the typical dual use potential found in the sciences: dual use research of concern. What is meant by “concern”? There are some types of experiments which would result in biological agents (or knowledge, technical equipment etc.) which are much more readily usable for non-peaceful purposes than the those resulting of the fast majority of experiments in the biological sciences. In other words, there are different risk levels of misuse of science associated with certain types of experiments. One possibility to categorize these types of experiments are presented along with the report of the Fink committee as I explained to you in my talk.

In your case there are several dual use aspects of your planned project: the biological agents used show some rather low misuse potential, but the genes/gene products you are plan to work with can at least in theory interfere with essential human body functions such as proper immune defense and the uptake of iron ions. Yersiniabactin genes are found in Yersinia species with Y. pestis being one of the well-established biological warfare agents of past offensive BW programs. BUT, that does not necessarily mean that any work on Yersiniabactin is forbidden now by international and national law or that research and development activities on that protein will only fulfil malicious purposes. That is by no means true! It is a matter of intent and the context of the work done. But in order to hamper any attempts of misusing scientific work on Yersiniabactin it is essential to perform a proper risk assessment. That must be done before the planned work will start. The risk assessment then should result in the implementation in all required biosafety and biosecurity measures well in advance before practical work will start.

In sum, following the iGEM rules, international (BWC!) and national regulations, good laboratory practice, good scientific practice as well as fundamental ethical principles (!!) you can conduct your project in a safe and secure manner. But you have to take the responsibility as a scientist.

We introduced our project plans to you. In your impression, are there any specific parts of our project that are of specific concern?

Interference with iron uptake in the human body in the course of counter-acting bacterial infections is challenging! You may target both, the pathogen as well as the host organism! Therefore, a carefully developed prevention strategy to minimize biological hazards is mandatory. One aspect would be the induction of multiple resistance against conventional antibiotics. In your case we are talking about standard antibiotics used in the laboratory, but not in the clinics. But anyhow, that is one thing you should keep in mind: altering the GMO’s susceptibility against antibiotics. Another security aspect is the intended interference with the iron uptake by those pathogens you are aiming at. You load your siderophores with gallium (Ga), fair enough, clever strategy. But what do you know about the amount of Ga which would be transferred into the human body once your therapeutic approach would be used under real world conditions? Any Ga intoxication possible? Think of elder patients having a lot of other malfunctions of their body! Is your method safe? Another issue would be the coexistence of several bacterial siderophores within the human body. Is there any possibility that other facultative pathogenic or even usually non-pathogenic microorganisms would re-use/”misuse” your strategy to survive within the host? That is a matter of different uptake strategies employed by different bacterial species and one should test that in the lab first, before you go live with your therapeutic approach. And of course, interference with ion (!) uptake per se could be an interesting strategy also for those actors looking for s.th. which might cause harm in humans, animals or plants.

For our safety assessment, we worked closely with Professor Heisig and Professor Aepfelbacher to receive an official license to conduct our experiments. We introduced our safety measures to you. What is your assessment regarding Dual Use Research of Concern? Are our measures sufficient?

So far as I can see it: yes! All what you have told me make clear that you did the right steps in the right sequence. First, you developed a challenging project which aims at a novel, fascinating therapeutic strategy to fight against nasty bugs (i.e., infectious disease-causing pathogens) by using a rather simple but theoretically quite effective method. But then, you were not just starting the experiments and look what might happen. No, you then went back to the desk and did a reasonable, comprehensive risk assessment involving the input from many experts. From our discussions, I learned that you are well aware of the promises but also the potential risks of your project. You did the required considerations well in advance – that is exactly what Good Scientific Practice and responsible conduct of science demands! You told me that you studied relevant literature and figured out what others have already published about the several aspects of your project (e.g., induction of antibiotic resistance, problems caused by iron depletion in the human body, work with Yersinia-derived genetic information). Once you have had reviewed the expert feedback and the information obtained from the literature you were re-writing some details of your project plans in order to achieve a maximum of biosafety and biosecurity precautions. In my view, your measures are sufficient. Especially, because we are not talking about large-scale production of the GMO generated in the course of your project nor clinical trials involving test with patients in a hospital environment. In these cases, there would be much more to think about. But that is another story to tell…!

To conclude the interview, what is your general assessment, we spoke twice about biosafety and biosecurity issues. In between our meetings we had time to implement your suggestions from our first meeting. Were we successful?

I am quite confident that you are conducting your iGEM project with a responsible and wholehearted attitude. You successfully performed the mandatory risk assessments and in addition learned a lot about biosafety and biosecurity. It was a great pleasure for me to guide you through the world of dual use research of concern and biosecurity issues. Together, we addressed the relevant points affecting your project and further developed your risk assessment. And last but not least: You are now practitioners in biosecurity! Congratulations from my side and all the best for the iGEM 2017 Hamburg University team!