Education and Public Engagement

In Australia, there has been a massive push for STEM (Science, Technology Engineering and Mathematics) education. This push has resulted in an increased exposure to children of the wonders science and technology can produce and change in our worlds. As an iGEM team and Science citizens of the world, we took it on ourselves to encourage that curiosity in the students of today. As a team, each of us spent time at various stalls and in group talk sessions to answer questions, demonstrate the possibilities of genetic engineering and to tantalize their inquisitive minds. Another aspect of our teaching practices were to effectively communicate our project to anyone, anywhere. Please read more on our Engagement page!

Law and Regulation

All therapeutic drugs that enter the market space in Australia must meet very specific and stringent criteria. As a team, we had to ensure that we were aware of these systems, and the work that would need to be done following our project to get our insulins on the market.

The Australian Government regulates therapeutics through the Therapeutic Goods Administration, which carries out its regulations following the Therapeutic Goods Act 1989. The classifications for a biosimilar state that:

• The biological medicine is highly similar to the reference medicine notwithstanding natural variability inherent to all biological medicines;
• There are no clinically meaningful differences between the biosimilar and the reference medicine in terms of safety, quality and efficacy.

Proinsulin is a human hormone which we have not mutated in any way, other than optimising the codons for E. coli synthesis. Therefore, we believe that our Proinsulin constructs will fall into this Biosimilar category. This means we will abide by the Australian Regulatory requirements by simply performing a Biosimilar Clinical Trial.

However, Winsulin will not fall into the above category, it means that we must perform a IV tiered clinical trial series in order to take it to market. Proinsulin on the other hand, will only require a Biosimilar series of tests to abide by the Australian Law and enter into the marketspace.

Another aspect of our project however was dealing with International Intellectual Property Laws. As a group, we had a series of issues that resulted in loss of work and progress due to the restrictions in place. As a result, we have since spent a tremendous amount of time reviewing current patents, in collaboration with a Patent Attorney from Maxwells IP, to ensure we are not infringing any claims. Please read more about how Law and Regulation integrated into our project here!

Product Design

For any project to work, you must consider all aspects of the product and how it will benefit society. In our case, we aim to alleviate strain on families who cannot afford or access insulin readily. For this end, we had to design our project in two main ways. The first, was that it was safe to use, and the second, was that it is easy and cheap to produce. For other aspects of the design that we had to consider, please visit our Design Page!

Obviously, we are aiming to synthesize a protein that can be used for human treatments. For this to be achieved, it must be safe to use in humans. Therefore, we had to ensure that we had only conserved mutations, or mutations that had been previously done and shown to have no adverse reactions during clinical trials. Luckily, other than general allergic reactions, we came across no mutations that had been linked to any adverse reactions in Proinsulin. For Winsulin, we do have to trial whether the 12AA C Peptide is immunogenic or whether it works. However, we ensured that the A and B chains of insulin remained homologous to the native human insulin sequence.

We also needed to design a product that would reduce post translational efforts. We hope that by making the method cheap and easy to follow, small scale manufacturers will feel more confident in picking up this product. To achieve this, we carefully considered of the type of excretion methods and vectors we would be using to achieve maximum yield and purity. To do this, we designed 3 expression systems across 2 bacterial species to compare and contrast the efficacy of mass production using each system.

Please read more about our project design here!

Social Justice

The more we worked on the project, the more social injustices we uncovered. Each corner of the globe seems to have a different issue. Whether it being simple accessibility to insulin as seen in China, India and most African countries, or a lack of information about the use and support networks required to cope with Type 1 Diabetes like in Brazil. Tragically, Americans, Singaporeans and many other nations alike leave their citizens with an inability to afford insulin, as the governments themselves do not subsidize it. We as a team felt it was necessary to talk to people to hear their own stories, and so we could better communicate the issues to an international audience. Furthermore, we aimed to take on the feedback we got from people about insulin and the issues they have in different countries to improve our Product Design.

Ethics

For a successful project, we must consider the implications of bringing a new, cheaper drug alternative into a market space. On one hand, we are elevating an imposed burden on millions of households that currently cannot access or afford insulin. To further ensure that we are meeting this goal, economic analysis on the current burden of insulin prices has been completed.

On the other hand however, we will ultimately be slashing the profit margins of those currently in the market in order to remain competitive to our lower, affordable price. Though indirect, this could impact the development of other much needed drugs or diagnostic tools, which these companies also develop.

Because of the ethical dilemma we are in, we spoke to a Bioethicist at Sydney University to better understand the implications of high costs medicines.

Safety

Primarily, above all else, we have to ensure that our insulin, a therapeutic product, is safe for all to use. All other efforts will not be worth it, if we fall short on ensuring our potential users’ safety. Therefore, we had to ensure that there was good research to support our understanding the insulin was safe in its native form, and that no other analogue or slight mutation induces any immunogenic reactions. From talking with a pharmacist, we found out that Endocrinologists are hesitant to prescribe biosimilar insulins, as when they switch to an analogue insulin, adverse allergic reactions can occur. We therefore designed our Winsulin to be different enough from the native form, that it would not classify as a biosimilar, but an analogue.

To ensure utmost safety, Winsulin must go through a IV tiered clinical trial set before it can be sold commercially. Human Insulin on the other hand, will have to pass a biosimilar test prior to commercial sales.

Survey Results