Team:Cooper Union/Ethics

“White paper” on our round table discussion on Biosafety, Biosecurity and Bioethical ramifications of the De novo Enzyme Mediated DNA Synthesizer and “Super Safety Strain” yeast projects.

In Attendance: Nolana Wong, Sara Wong, Lily Lin, Rebecca Poch, Hua “Joe” Fung, Jiwoon Park and Wilfrido Castillo (IGEM Team Members)

Special Guest: Keith Comito (MA in Bioinformatics and Software Developer)

Moderator: Oliver Medvedik (Instructor)

Background: Throughout the summer we have been having impromptu discussions amongst the team regarding biosecurity and biosafety implications of developing a technological platform that would enable easier, faster and cheaper synthesis of DNA. The safety implications of having a device that will essentially permit a broader direct participation in synthetic biology was realized early on in our project. A more nuanced consideration regarding bioethics was also realized early on regarding the development of a “safer” yeast strain that has a programmable lifespan and the potential for this strain to be used to limit access to certain applications, in contrast to the DNA synthesizer technology which may present dangers in the opposite direction. In addition to ad hoc discussions, we decided to summarize our thoughts in a the form of a publicly available written “white paper” and invited an outside participant, Keith Comito, to provide additional insight from the field of software, to see if any overlaps may exist in that field with our projects, particularly the yeast safety strain.

Meeting Minutes:

Oliver: What are the security issues regarding DNA synthesis as it is currently practiced and how are they being addressed?

Joe: My understanding is that most synthesis is via a vendor, such as a company, which sequences are submitted to. They may then do checks on the submitted sequences, so that is a potential check currently.

Wilfrido: There are problems with the current checks as submitted sequences may still circumvent the checks.

Jiwoon: Even if guidelines are hard to enforce, we should still work on implementing a version. This would at least make people aware of the biosecurity issues and have everyone agree to commonly accepted social norms.

Rebecca: Some ways to circumvent the current system may involve sequences that are not in databases.

Oliver: There are uses of software that “red flag” suspicious sequences, but limitations for this, as small sequences, ie. Less that 200 bp may slip through the cracks. This is also a voluntary system, that is not universally adopted. Can you think of any potential hazards regarding the synthesizer project and methods to ameliorate this.

Joe: Obviously having an easier ability to synthesize DNA may make this technology more accessible to wrong individuals. One potential method to ameliorate this may be to have the device send the sequence to a distant site that checks the sequence to validate its approved synthesis. This may be difficult to implement though, as this may be circumvented, or the technology circumvented.

Wilfrido: I don’t think the risk is presently that high. The potential for good applications of this technology far outweighs any potential for misuse.

Jiwoon: There should be some sort of regulatory framework, even if it is not perfect, just so that we have a basic agreement as to what constitutes a proper use of the technology.

Lily: The other danger is that over regulation may dissuade the proper use of the technology, such as potential cures.

Oliver: What about other regulatory "choke points", such as modified dNTPs, rather than the device itself.

Joe: That may be a good regulatory point at first glance, but there are many variants of reversible protective group dNTPS that may be more easily synthesized. So again, we are back to a practical difficulty in regulating the technology.

Oliver: These issues are also further complicated by the fact that there are no universally agreed upon agreements around the world regarding biosecurity regulations. Let’s turn to the ethical implications of the development of a safe strain of yeast that has a programmable lifespan for biosynthetic pathway cloning. Monsanto’s sterile plant technology that creates sterile seeds as a method to create a bio-contained strain come to mind. The blow back to this technology was regarding the potential corporate misuse of this technology to create a monopoly on valuable crop plants, as this would now make the farmer beholden to one corporation for their crop, resulting in the moniker “Terminator Seed”. We’ll hear from Keith to see what, if any, crossovers there are with software technology and legal issues as regards the end user and companies.

Keith: One current software controversy that can be a corollary to the yeast strain technology is with regards to shareware that is only available for a limited time, after which the user needs to pay a fee if they wish to continue using the technology.

Rebecca: Such as having longer lived strains being available for more money, to promote longer growth cycles for biosynthesis in a fermentation vessel.

Keith: Other issues that are controversial is by having software that has certain features locked, so that end users have to continuously pay extra to access them.

Nolana: How would this detail apply specifically to the yeast strain that we are developing? It is clear that having a strain that has a limited lifespan that only produces, for example, a life-saving drug, would be a clear example of how the strain could be misused, but how could specific “feature” be locked?

Oliver: Well, the application of the cre-recombinase system that you are using to inactivate telomerase, may also be used, via a proprietary drug fro example, to activate another “hidden” gene in the strain for example, that has some useful function, or maybe makes the strain more “improved.

Sara: There are also issues of circumventing the safety technology, just as with the DNA synthesizer. Of course, that will always be the issue though with regulations, technology and people attempting to circumvent safeguards.

Meeting Summary:

As our projects raised several important issues related bioethics, social justice, safety, security, and intellectual property rights, a final meeting was held to record our ongoing thoughts on these matters for public record, so that a continual discourse my be had. Our discussions throughout the summer were kept informal. This allowed for, we beleive, more open ended discourse. Overall, after exploring these concerns, we felt that the need for greater progress in synthetic biology, currently outweighs any potential risks inherent in the technology. And that furthermore, the potential benefits deriving from the the continued development of our projects also far outweighs any potentials for misuse. By making the record of our discussion public, we hope that this will both stimulate further talks, as well as open up any constructive criticism, in case that there are elements missing that anyone feels have yet to be addressed. We hope that our example serves as a model for continued transparent discussions on these weighty topics and that such sessions continue to be held out in the open, rather than behind closed doors.