Teaching Responsible Conduct of Research (RCR): A Resource Guide for Professional Science Master’s Degree Programs
Case Studies from Biology and Biotechnology
Case: Recombinant Toxic Substances
Discipline: Biology and Biotechnology
Ethics Topic: Biosecurity
Case Subject Matter: BioPunk
Controversy: Recombinant Toxic Substances
Authors: Brooke Ethington, Tyler Holt
Biosecurity Background Information
As biological techniques become cheaper and easier to perform, and information becomes increasingly accessible to anyone interested to find it, the chance of misuse of these techniques and information increases. The concept of dual use research is that legitimate scientific inquiry has the potential to be used out of its original context for inappropriate usage up to and including development of bioweaponry. As information is absorbed and adopted into the greater community the scientific and governmental communities lose their controlling positions over the research questions, which are explored, the methods used to explore them, and the security of the information once obtained. It is clear that the management of dual use research cannot be left solely in the hands of government regulators; blanket restrictions designed to manage research activities from academia through the biopunk movements may require sacrificing the speed and freedom under which current scientific inquiry is conducted.
The responsibility of the researcher to prevent misapplication of methods or findings is becoming a serious ethical issue. Investigators are in a unique position; as subject matter experts they are the most qualified individual to identify potential dual uses for the techniques and results of their work. Awareness of this potential and a real consideration of the repercussions should their findings be published must be weighed against the cultural (and often financially driven) incentive to “publish or perish.”
The first consideration for dual use research is the potential for a technique to be adapted for the development of bioweapons. Bioweapons have been widely used throughout history; most bioweapons were developed under the watchful eyes of the scientific community and adapted from simple and widely used techniques. In 1925, the Geneva Protocol prohibited use of bioweapons and this sentiment was ratified by the US senate in 1975. In 1975 the Biological and Toxin Weapons Convention (BTWC, or more formally The Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction) was also enacted. This treaty prohibits the development, production, stockpiling, and acquisition of biological and toxin weapons, and required the destruction of existing inventories and delivery devices. As with the scientific community, the question of responsibility, accountability, and enforcement has not been sufficiently explored at the nation’s level.
6th Century BC / U / Water poisoning using fungus / Assyria1710 / U / Introduction of Plague / Russia
1937 / D / Anthrax, plague, cholera / Japan
1941 / U / Tularemia / Soviet Union
1941 / D / Anthrax, tularemia, botulism, brucellosis / USA
1942 / D / Anthrax / UK
1972 / D / Typhoid / USA
1978 / U / Cholera, anthrax / South Africa
1978 / U / Ricin / Bulgaria
1991 / U / Botulism, anthrax / Iraq
2001 / U / Anthrax / USA
Table 1: Highlighted history of bioweapons development (D) and use (U). NOTE: this is NOT a complete list!
The future of bioterrorism is moving towards the home brew methods. Several examples of dual use research have been reported using methods, equipment, and materials taken completely from online resources including synthesis of the polio virus and influenza viruses. One study, which caused concern in the community about the potential for dual use research described improvements of drug delivery via aerosol methods, which could potentially be used for the widespread delivery of toxic agents or harmful biologics.
Dual use research has been used to break the law in a non-conventional way. The biopunk movement is a growing trend. A biopunk is a hobbyist who experiments with DNA and other aspects of genetics. These individuals perform high-tech biological experiments in their closets, basements and garages. They also find innovative ways to inexpensively produce the necessary equipment for these high-tech experiments. An example of one of these experiments is the transfection of tobacco plants with THC gene found in marijuana. They found that it was quite possible to achieve THC expression in the transfected tobacco plants. The study is an example of research that could be duplicated by biopunks in order to circumvent the law. It shows that not all people are interested in technological advancements in biology are interested or willing to create bioweapons.
There is now the question of what to do about information pertaining to biological research. Researchers could self-police to ensure that only responsible and trusted parties have access to their data. Journals and institutes could suppress certain information in papers such as materials and methods. Researchers could choose not to publish in order to avoid the information getting into the hands of dangerous individuals. All of these choices will end up in the impediment of scientific findings.
But something must be done to safeguard the public.
Dual Use Case Study: Rehashed
Most college students know that there is nowhere good to buy weed on campus. So they invented it. Two student roommates were riding the golf cart around campus after their biotech class and were all fired up about transfection methods and all of the cool things that they could make if they had the supplies. Then it hit them- they could do this.
So they went to their best friend- Google. Of course, everything they could ever ask for was there and they were so excited. They converted one of the bathrooms in their apartment into a wet lab using equipment and supply purchased online and were able to save quite a bit of money by making their own equipment, like the compound microscope they made by removing the camera off of a webcam and turning it upside down; $10- score!! One of their dads even came and checked out their little operation and was really proud of the lab setup they had put together- it was just like when he was in college building CB radios with his friends and hacking the radio waves.
The two students practiced a few times on bacteria they grew on potatoes and then they had this great idea to make a glowing rose bush for one of their girlfriends. So the time had come!! They had only put between the two of them about $200 in investment and they were ready to take the leap and try something that would make them some money back. Just outside of their apartment window there is this obnoxious ivy plant that grows clear across the window and makes it hard to open. They decided to take a clipping from this ubiquitous and innocuous plant and transfect it with the genes for THC1 (not hard to find, look on Google).
They researched the literature and discovered this had never been done before, it was novel, and it had both commercialand scientific value. They found lots of support on some BioPunk websites and Blogs, and actually attended a few seminars where they were able to tweak our technique to get it just right. They grew their new friend “Potty the Potted Plant” big and strong, and got ready to test it out. They dried some leaves and processed them according to the instructions they found on line. So, they smoked it, as a trial run- they couldn’t sell a product without ensuring its safety and efficacy. They suffered no ill side effects although one of the roommates was sure that there was a raccoon trapped in the room with them-they attributed that to not drying the ivy thoroughly. Anyhow, once they ensured that it was perfectly safe to use, they began taking clippings and selling little houseplants to their fellow students.
With the money they made they were able to reinvest into their enterprise and purchase some upgraded equipment. They took a poll of our fellow students asking what drugs they would like to be available through either inhaled or eaten vegetation; top requests included contraceptives, acne relief, and allergy relief. Some of the more mischievous students suggested that they transfect plants to produce botulism toxin or morphine. They had started tinkering around with different herb types and had some promising results so far. Several of their friends have asked if they could help them to develop these ideas and then went to brag about their work to some professors.
Here is where the trouble comes in… One of their professors approached them the other day and told them off for breaking the law by providing THC to students even though it was not in marijuana. He commended the students for being so enterprising and for moving into further interests to meet demand, but he felt that he would have to turn them in to law enforcement citing that we were performing research on their friends and dealing drugs. Another one of their professors suggested that they file a provisional patent and write a paper to submit to a journal. They are too afraid of the legal implications to do either of those things.
They just applied what they had learned and were smart enough to capitalize from it. Isn’t the whole point of Socratic method and the university system to give students the tools to freely investigate and to foster an environment of entrepreneurism and creativity? They never wanted to go to jail.
Sirikantaramas S, Morimoto S, Shoyama Y, Ishikawa Y, Wada Y, Shoyama Y, Taura F. 2004.The Gene Controlling Marijuana Psychoactivity: Molecular cloning and heterologous expression of Δ1-tetrahydrocannabinoic acid synthase from cannabis sativa l. Journal of Biological Chemistry. 279: 39767-39774
Ethical questions to consider regarding Dual Use research:
· Whose responsibility is it to monitor what research is published, and what equipment is sold?
The vendor and the publishing journals should be responsible for monitoring what they sell and publish. If there is something blatantly dangerous that they are providing than they should prevent that from being available. Unfortunately, as of today, they are not responsible.
· Is it acceptable to publish research that could be used for bioterrorism?
Journals should not publish research that could be used for research unless they omit information that could help potential terrorists to duplicate the experiment such as the materials and methods sections. Researchers that are known and trusted should be allowed to have access to the information if they are planning to conduct further research.
· Should you publish techniques to purify or create recombinant production of toxins?
It is a moral obligation of journals not to allow dangerous information to fall into the wrong hands. Morally giving someone the information that they need to create a toxin that could kill thousands of people is very close to creating it yourself.
· Should you allow universities to hold potential bioweapons?
In this situation one should consider the potential consequences. Universities do not have the policies and procedures in place to properly secure their research materials that could be used as bioweapons. If they had the proper security than perhaps it would be a different situation but as of now they should not have these potential bioweapons.
· Is it appropriate for policy makers to limit researchers in dual use research?
The distinction between morality and the law is important to consider in this case. In many cases, the law has not limited the research that scientists can perform. But because it is not necessarily illegal, does not mean that it is not immoral. In some circumstances the research that one conducts has beneficial possibilities that outweigh the bad but in many situations they do not.
· Whose responsibility is it to determine whether or not research could be used for malicious intent, and whether or not to publish?
It is very difficult to determine what is “wrong” to publish due to the fact that many people disagree about the quantification of “beneficial” or “bad” in this case. The journals need to have an ethics committee in order to determine what information should be published and what should not.
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