Team:BOKU-Vienna/Safety

Safety

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Safety.


In assessing the safety aspect of our project idea, we elaborate three policy goals in synthetic genomics:

    • Biosecurity.
    • Laboratory safety.
    • Protection of the environment.[1]

Biosecurity.


Reverse transcriptase is the key enzyme in the mechanism that causes HIV to be immune evasive. As the virus injects its RNA into the host cell, reverse transcriptase writes an error-prone cDNA replicate, which is then integrated into the genome. These errors are inhibited by the cDNA strands and are the cause of the disease’s resilience. Therefore, it is possible - though unlikely - that D.I.V.E.R.T. could be used to engineer a pathogen and make it similarly immune evasive. We assume that this could not happen on accident and would have to be done on purpose. Safety in the field of DNA-synthesis is very important because it is much easier to order synthetic DNA online and construct a virus from it, than isolating a pathogenic strain from the environment.[1]
For that reason, several different gene synthesis firms founded the international gene synthesis consortium (IGSC) to come up with a harmonized screening protocol, vetting both the sequences and the customers that place the order. Every ordered sequence is aligned with the genomes of a number of organisms of concern. The IGSC maintains a database of sequences from organisms listed on the US Select Agent list, the Australia Group List, and the European Union’s list of controlled species that are used by all members to screen for potential biohazards. The gene synthesis company Blue Heron Biotech also claims to use a combination of the IGSC database and Craig Computing’s BlackWatch software, which is an aid in running searches for pathogenic sequences.[2]
At IDT and other IGSC member companies, all orders for double stranded DNA are screened against the pathogen database. If the best BLAST hit from a sequence is identical to one of the sequences in the database, the order is reviewed manually for safety. As for customer screening, all customers have to supply their identification data to the gene synthesis firm. If the ordered gene sequence is from the pathogen list, IGSC companies first confirm that the customer belongs to a research organization and that the ordered sequence is consistent with their research activities. If any suspicion is raised, the gene synthesis companies may require their customers to supply further documentation, like a curriculum vitae or clearance from the Institutional Review Board. On occasion orders may be denied, because they are deemed to be dangerous or pose a risk to the community.[3]
The IGSC claims to represent around 80% of the global gene synthesis capacity. Many gene synthesis companies that do not belong to the IGSC have different screening protocols, appropriate to national law[4], or none at all.[5] While the IGSC database is routinely being updated, most gene synthesis firms will not divulge on whether these security measures are going to change in the near future, however, two companies claimed that they are not planning on any significant changes.[6] Though with increasingly effortless methods like D.I.V.E.R.T. on the horizon, allowing researchers to change their synthetic DNA in-lab, the screening process may at some point have to be modernized.

Protection of the environment.


Likewise to any genetically modified organisms (GMOs), cells carrying our D.I.V.E.R.T. cassette could prove a risk to the environment in some cases. To assess these cases is almost impossible. For once, mutating an antibiotic resistance could potentially bring forth a new super-resistance, possibly endangering the environment, if the GMOs are released. In contrast to conventional methods of directed evolution, D.I.V.E.R.T. causes mutations not in the whole genome, but in a target gene only. Therefore, it is very important to assess the risks beforehand in any application of D.I.V.E.R.T., depending on the specific gene that is being mutated. However, D.I.V.E.R.T. is not meant to be released into the environment. Its application is in screening processes only, happening inside the lab in closed systems, such as shake flasks. Therefore, standard lab safety precautions will eliminate any threat to the environment, if done correctly.

Laboratory safety.


Working in a synthetic biology lab unavoidably bears some risk to the operator. Therefore, it is very important to adhere to the safety rules to keep those risks at a minimum. Before starting off with any wet lab work all members of our iGEM team were introduced to the standard safety rules.

Those rules addressed the following:

  • Personal protection: wearing long pants, closed shoes, lab coats and gloves while working; tying long hair together; not wearing jewellery; wearing safety goggles when using UV-light.

  • Working area: no smoking, eating or drinking in the lab; cleaning and disinfecting benches before and after work; decontaminating equipment after usage.

  • Chemical safety: handling and appropriate storage of chemicals and toxic compounds

To be aware of potentially hazardous situations we might face, and most of all to learn how to react to them properly, we were also shown and demonstrated the safety gear our lab was equipped with including a first-aid-kit, an emergency shower, an eyewash station, a fire extinguisher, a fire blanket as well as a gas and power emergency switch off. Additionally, we were given the contact details of the first aid personnel and shown the emergency evacuation plans. During our work we followed all iGEM’s safety policies.

[1]: Garfinkel MS, Endy D, Epstein GL, Friedman RM. Synthetic Genomics: Options for Governance (2007)

[2]: See Craig BlackWatch's Website

[3]: International Gene Synthesis Consortium, Harmonized Screening Protocol: Gene Sequence & Customer Screening to Promote Biosecurity

[4]: see eg. here on US export-law.

[5]: Carter S. R, Ph.D. and Friedman R. M., J. Craig Venter Institute, DNA Synthesis and Biosecurity: Lessons Learned and Options for the Future (2015)

[6]: E-mail correspondence with Dr. Adam Clore, Technical Director of Synthetic Biology at IDT, Blue Heron Biotech and two other gene synthesis firms