Team:BABS UNSW Australia/Practices

Communication Strategy

All our outreach initiatives also involved communication of our project. We delivered presentations to various groups, from high school students to university students and academics. At first glance, and even at second glance, the end goal of introducing bacteria into mammalian cells can sound alarming. We had three strategies to convince people of the validity and safety of our project:

  1. Branding: Word choice can have significant impact on public reception. By using terms such as “entry into cell” rather than “invasion,” and “endosymbiont” rather than “parasite” the project was made to sound less sinister.

  2. Relating to topical knowledge: Public awareness of the importance of our microbiomes and of microorganisms in general has increased rapidly over the past few years. By selecting endosymbionts already found in the gut microbiome (Lactococcus) or commonly found in natural environments (Synechocystis), we hoped to make our audience more comfortable, due to the relatively high exposure and familiarity we already had with these organisms.

  3. Safety mechanisms: Finally, we explained the several levels of biocontainment and biosafety strategies. We had a three-tiered approach to ensuring neither organisms or genes would be released into the wider environment. Near the end of our project, we also assured people that we were not going to test our invasion devices because we were not satisfied that we had sufficiently tested and characterised our Cre-lox and toxin-antitoxin system.

Biosafety Report

As explored within our Final Safety Report beneath the biosafety menu, biosafety considerations have been a pivotal aspect of project Endosynbio due to the risks associated with our work and the fact that we're new to both synthetic biology and the iGEM competition. The report below was compiled in order to discuss some of the broad philosophical themes in synthetic biology pertinent to our work with pathogenic genes. We felt that, because we are so green, we could offer a valuable fresh perspective on the way in which we think about and practice synthetic biology, particularly in relation to the interaction of chassis with donor genes. In this way, we endeavour to encourage new ways of thinking which we believe will increase biosafety awareness and safe design.

Click on the report to read further!

Make Your Own GMO Workshop

We collaborated with the Australian BIOMOD team and ASPIRE (a UNSW high school outreach program) to run a workshop for students from across several rural and low SES schools. After a rudimentary introduction to cell biology and genetics, we explained design of basic genetic circuits with a focus on promoters and protein-coding genes.

a quick debrief on DNA and gene expression

Students had the opportunity to select from a list of real-world problems, and then design their solution by picking a chassis organism and choosing genes to add to it. Most groups designed hardy, nutritious plants to solve world hunger. Only one group chose a different problem - they aimed to solve boredom by generating a cow with endlessly regenerating limbs… “imagine a cow with like 100 legs!” Students enjoyed discussing all the possibilities, and those who wanted presented their creations to the group.

GMP: a genetically-modified plant to feed the world

A quick survey post-activity told us that students enjoyed the activity, and found the challenging aspects enriching. Some of the favourites of the genes available to them were the flagella-encoding gene and the apple-scented protein gene.

We also assisted the Biomod team in running a DNA extraction activity. By combining both activities into one session, we enabled students to participate in both the conceptual and hands on aspects of genetic modification.

If you'd like to have a fun and interactive class on GMO's (and maybe save the world) feel free to use the following resources.

Australian iGEM meet up

We hosted the first meet up for 2015 Australian iGEM teams. 75% of Australian teams (i.e. 3 out of 4 total) attended. It was a great day to meet, commiserate, and share our work. Each team gave a presentation about the project, and faced question time from other teams, advisors, and a past iGEM judge.

Some of the meetup attendees from UNSW, University of Sydney and Macquarie University

In the aussie tradition, we finished the day with a barbecue and some beers.

The Great Debate

Creating Superman - is it ethical to genetically modify organisms?

Across the world GMO technology is a hotly debated topic with fierce proponents on both sides of the fence. Given that we were dealing with these issues on a daily basis we thought a great outreach project would be to have the ethics of our science contested in a verbal boxing ring. To do so we organised “The Great Debate” in collaboration with our schools society Babsoc. On the table was the broad spectrum topic “Creating Superman: Is it ethical to genetically modify organisms?”. The two teams were sourced from enthusiastic Science undergrads who went head to head on a balmy Friday afternoon. A range of convincing arguments were communicated by both sides. Some of the team's’ key points are summarised below.

Affirmative

  • Potential risk-benefit analysis, with examples of how such technologies have helped humanity in the past
  • The near limitless potential of genetic engineering, and how with it many of the world's current problems can be alleviated. Examples included achievements such as the use of Golden rice to combat vitamin A deficiency.
  • The foundational benefits of how research into GMO’s will expand our basic understanding of the universe and our place in it.
  • Honouring nature by re-using its pre existing solutions.
  • How addressing this issue with an anthropocentric attitude will assist the growth of humanity.

Negative

  • Argued how the ethics of this debate are often looked through only the eyes of humans and not objectively by nature; a case against anthropocentrism.
  • “Just because we can doesn’t mean we should”, tampering with the natural world is not a trivial matter and should not be taken lightly.
  • The Genetic Arms race, the use of toxic genes/chemicals leads to the rise in resistant organisms. This was discussed in length with regards to genetically modified crops, in particular BT corn and RoundUp ready varieties.
  • Mother nature always finds a way, this argument was used in two contexts. First of all, if there is a problem in the world somewhere a solution to that problem already exists and instead of artificially recreating that solution we should be tapping into what is already there. Secondly it was used as argument in the “Genetic Arms Race”.
  • The science of molecular biology as a whole is significantly unpredictable.
  • If a transgene escapes its host confines it is essentially impossible to get back, there are no second chances.

After the teams had concluded their cases the verdict was decided by audience vote. In an unexpected turn of events the voters were swayed to the side of the negative team. Perhaps this is an good case in point of the importance of how we as scientists, present our cases in a public forum.

Reflection

Overall the event was both entertaining and insightful. In the future we would look to change the following aspects.

  • Source speakers from a wider range of fields including social science, philosophy and law.
  • Record or live stream the debate to facilitate a wider audience.

The Negative team in full flight

Encounters of the IP kind

Our project is definitely on the science-fiction end of the feasibility spectrum, and we acknowledged early on that we would not be able to generate any immediate applications from our work. Instead, we aimed to lay the groundwork for further discovery. However, after several months of working with pseudoknots, it occurred to us that they may be patentable, and we explored the possibility.

Is it possible?

According to Australian patent law (closely modelled from the American system) for an invention to be eligible for patent protection it must fit certain criteria. It must be patentable subject material, novel, useful, and must be non-obvious/involve an inventive step. We believed our pseudoknots fit all the criteria.

Patentable subject material

  • Despite recent court cases questioning the patentability human genes [ref myriad], the pseudoknots are patentable subject material. They are viral in origin, and are sufficiently modified (start codon removal) to be considered synthetic.

Novel

  • A preliminary prior art search showed no patents or scientific literature describing the adaptation and use of pseudoknots we proposed. The only papers describing pseudoknots described their role in viruses. Additionally, other protein expression timing devices available function at the transcription level – pseudoknots would be the first offering translational control.

Useful

  • The pseudoknots could be useful across a range of genetic circuits in delaying translation of protein. This has potential to increase yields or efficiency in several biotechnology processes.

Inventive Step

  • We believed we had a case for an inventive step – not only did we modify the sequence, but we used the pseudoknots in different organisms, in different locations of the genome and for a different purpose. We removed stop codons, localised them in between open reading frames (instead of within them) and used them for delaying protein expression, not frameshifting, in bacteria instead of viruses.

Why?

Patent protection would enable the commercialisation of our invention, and owning intellectual property related to research can stimulate investment. We could more readily procure funding from an interested party if they knew their investment would be protected. In biotechnology, patents are the cornerstone of any business or commercial enterprise – products require large research costs, and are often reverse engineerable. For example, anyone with access to our pseudoknot sequences could synthesise the genes for themselves. For these reasons, to achieve a return on investment patents are essential.

How?

We consulted with the university business development team (UNSW Innovations) and an intellectual property lawyer. They did not have specific biotechnology knowledge, therefore could not confirm the patentability of our invention. However, they agreed it was possible, and described the actions we would have to take to secure a patent.

  1. Write and lodge a provisional patent
    1. The provisional application contains as much information as possible, given current research. The full application is the final version
    2. The lawyer suggested that we could write the provisional patents ourselves.
    3. During the following year, find and investor/sponsor to cover the cost of the full patent application and further research costs
    4. Register a company to facilitate joint patent ownership.
  2. Lodge PCT application within one year.
    1. At this stage, a patent attorney must be payed to write the application. Wording must be precise, and biotechnology patents are often hundreds of pages long.
  3. Lodge national phase applications (in desired countries) within 18 months of the PCT application.
    1. Each country filed in incurs an extra cost. Prior to filing, we would have to determine addressable market sizes as well as consider distribution channels of any partners we had attained.

Our decision

We decided not to pursue patent protection for the following reasons

  1. Difficulty- Drafting a provisional patent would require significant research and writing hours. In addition, we would need to find investors to support our full patent application and future development.
  2. Cost
  3. Disclosure
    1. Another issue we faced was the level of disclosure which had already occurred. Because the invention was developed in the context of the iGEM competition, we had freely discussed it not only amongst ourselves, but with friends and colleagues. In all likelihood, this would not have posed a problem. However, there existed the legal possibility that someone could come forward and claim we did not have a novel invention, due to that previous disclosure. We did not suspect any ill motives, but it is important to consider potential outcomes such as these when an undergrad research project suddenly turns into a potentially money-making venture.
    2. The iGEM competition is fiercely open-source, and it is difficult within that context to generate intellectual property. So we ask, is it truly possible to have an open-source model (based off the software community) in synthetic biology? Start up costs and lab consumables can easily yield project budgets ranging in the tens of thousands. Without IP generation or protection, future funding is limited to sponsorships and government grants. Corporate/industry investors will not fund a project that does not promise a return - and in the biotech industry, without patents this is very difficult to do. The open source model has been possible at the small, undergrad level due to the generosity of corporate sponsorships and (in our case) universities. However, does the open source model limit synthetic biology to the small scale?