Integrating Human Practices
Our Human Practices Journey
Overview
To address the increasing demand for Paclitaxel, the early stages of our project focused on improving the yield and efficiency of the current semi-synthetic pathway. As we communicated with stakeholders, we realised there were 3 main improvements we could make to our project to meet their concerns and desires. We grouped these improvements into 3 iterations to increase our project's potential impact. Each iteration had a central theme as a result of engaging with different stakeholders.
The benefit of focusing on one theme helped us efficiently develop a production pathway that was more responsible and good for the world. It expanded our project beyond just meeting demands of Paclitaxel, and towards improving the sustainability of how that demand is met. We have also been able to incorporate principles of green chemistry, to minimise our projects environmental impact. These changes included the pathway itself, down to how reagents are obtained and how waste products are reused. We were also able to work with industry professionals and investors to incorporate their feedback on how to best scale-up our pathway commercially to enact positive change.
In summary, by engaging with relevant communities and industry professionals and integrating their advice, we have been able to develop a project that is responsible, and good for the world. The integrations have changed how we carry out our lab work, how we execute our overall project, and its overall purpose. As a result, we have been able to align our project with the values of potential stakeholders, the communities affected by Paclitaxel production and those of iGEM.
Iteration 1: Improvement of current Paclitaxel production to help meet increasing demands
Overview
The first stage of our project saw us improve upon how Paclitaxel is currently semi-synthesised. It is produced through combining precursors found in the Yew Tree's leaves with a chemically synthesised side chain. We sought to optimise the biosynthetic pathway to produce Paclitaxel's side chain by co-localising the rate limiting enzymes (PAM and TycA) onto our protein scaffold Assemblase. To do this, we consulted with key experts that have used a similar hexameric scaffold, and protein researchers. Their experience was critical in helping design and troubleshoot our project to ensure we could scaffold these enzymes. In this iteration, we also sought to better understand the Paclitaxel market and whether what we were doing was needed by society. Part of this iteration saw us communicating with a government body, that helped propel our project towards the next iteration - improving the sustainability of Paclitaxel production.
Gilberto Lopez
Editor-in-chief of the Journal of Global Oncology
Gilberto Lopez helped us understand the Paclitaxel market, and the eventual impacts of our work. We were worried that our work would have little impact, due to the introduction of second generation Taxanes, that may replace Paclitaxel. Gilberto however assured us that Paclitaxel is too well ingrained into chemotherapy to be replaced within the next few decades, and that these next generation Taxanes are derived from Paclitaxel itself.
Integration
Dr. Lopez helped shape our project’s direction, and we kept his words in the back of our mind throughout the project - Paclitaxel is here to stay. Changes to our project were designed with a long-term focus, as it was important to consider and address potential impacts of our project.
Paclitaxel will continue to have a role (in chemotherapy). It is established in too many diseases for it to disappear in the next two to three decades.
Dr. Lopez
Peter Gunning
Former Chair of the NSW Cancer Institute Cancer Research Advisory Committee, Founding chair of Bio-Link Pty Ltd. UNSW
Professor Gunning was integral to better understanding the importance of Paclitaxel as a chemotherapy agent. He helped bring to our attention that a large number of cancer patients will require the use of Paclitaxel in their treatment plan. He not only reaffirmed that Paclitaxel is a crucial drug, but also that it will only increase in demand as time goes on. We learnt of improvements to Paclitaxel that Scientists are developing, such as Taxoprexin and Opaxio. There is also significant research showing that Paclitaxel could be used to treat more than just solid tumour cancers. All this cements the importance of Paclitaxel, and hence the importance of our work.
Edward interviewing Professor Peter Gunning
Integration
Through Professor Gunning, we were able to realise our vision that there is a need for more efficiency in Paclitaxel production, in order to meet current and increasing demands.
70% of chemo patients will require the use of Paclitaxel at least once throughout their treatment process.
Professor Gunning
Nga Tien Lam
Researcher at the University of New South Wales
Nga has had previous experience working with the Hexamer scaffold system. She helped us determine the viability of attaching the enzymes involved in Paclitaxel semi-synthesis.
- She confirmed the compatibility of the 2 enzymes we planned to attach - PAM and TyCA – with Assemblase
- She recommended that we conjugate the scaffold and enzymes using the reaction conditions of our enzymes and not Assemblase. This is because of Assemblase's thermal and chemical stability.
- The sizes of the enzymes were not too large and hence should allow the structure some flexibility in movement.
- Nga asked us to explore whether there was a benefit to attaching the enzymes to Assemblase through either mathematical or molecular dynamics modelling.
Kevin and David meeting Nga
Integration
Nga's advice was integrated into the design and execution of laboratory work, specifically experiments on the biosynthetic Paclitaxel production pathway. It also pushed us to explore molecular dynamics modelling.
- We explored the application of last years mathematical model. Attachment of our enzymes PAM and TycA to Assemblase saw a 6 fold increase in product yield.
- Commencement of molecular dynamics modelling and simulations to understand the flexibility of the structure, and whether it could accommodate for the enzymes PAM and TycA.
- Changes were also made to our conjugation protocols. Moving the reaction conditions from matching Assemblase to matching that of our enzymes. These resulted to changes in Salt Concentration, Buffers, pH, and Temperature of conjugation conditions.
- Preparation of plasmids and vectors to carry out the project.
The similarities in reaction conditions is not only beneficial to your research but also something that pharmaceutical companies may appreciate.
Dr. Nga Lam
Marc Wilkins
Founding father of the field of Proteomics, protein researcher at UNSW
We came to Professor Marc Wilkins with a problem - the tetrameric structure of PAM may result in difficulties in scaffolding onto Assemblase.
To increase the chances of our structure forming, he recommended that we investigate providing more space for Assemblase to fully assemble the PAM tetramer.
Integration
We increased the length of the GSG linker, increasing the distance between the ends of the subunit as well as the flexibility of the linker.
This allows large enzymes to be anchored on to the scaffold without having to deal with excessive steric hindrance.
He also recommended that to test the formation of the tetramer, we could use a cross-linking SDS page. Whilst we did not explore this assay as we continued to have troubles with expressing PAM, it was useful information to have for future teams, or if we wished to expand upon our work.
The tetrameric nature of PAM could be a problem, but if you figure out a way to give the structure some space, it could work.
Professor Wilkins
Why we moved to the next stage
Pharmaceutical Benefit Scheme
Manaf Al-Momani, Assistant Director of Price Changes section in Paclitaxel
Through Manaf Al-Momani, we realised that despite the importance of Paclitaxel, the drug undergoes an F2 price disclosure scheme in Australia. This essentially means that pharmaceutical companies must disclose all the costs that go into producing Paclitaxel to the Government, bringing the price of the drug close to its market value.
Essentially, we realised that improving the current semi-synthetic method of Paclitaxel production would not be making as positive or large of an impact as we once thought. Whilst a more efficient production method would help meet increasing demands, we would not be using Assemblase to address more important issues such as sustainability.
Integration
After our conversations with PBS officials, we began to expand our projects focus towards addressing more critical issues in Paclitaxel production.
However, we continued our work on improving the current semi-synthesis pathway, as Paclitaxel is still expensive in other countries like America, and a reduction in production costs could help reduce this. Furthermore, it would still benefit Australia, as for every $1 we reduce in the cost of Paclitaxel, it frees up $500,000 for the Government to reallocate.
For every $1 you reduce in the cost of Paclitaxel, you free up $500,000 for the Government.
Mr. Manaf Al-Momani
Iteration 2: Making Paclitaxel Production Sustainable
Overview
In response to the feedback we received from our previous iteration we expanded our purpose towards addressing environmental problems in the production of Paclitaxel. This expansion of our project's scope meant we could create a more meaningful impact on Paclitaxel production, that was responsible and good for the world. Additionally, focusing on sustainability brought more local relevance to our project as we collaborated closely with people near Australasia.
We identified 4 key problems in Paclitaxel production that we sought to address:
- Paclitaxel demand needs to be supplemented by logging the yew trees and directly extracting Paclitaxel from the bark. This method is more attractive to companies, as it requires less chemical synthesis steps and hence is cheaper. However, this results in the logging and destruction of Yew forests and plantations, contributing to the un-sustainability of the current Paclitaxel Production pathway.
- In the current semi-synthesis pathway, rare and unsustainable reagents are used, such as Baccatin III, found at 0.0005% in the yew tree leaves and 10-DAB found at less than 0.1% in the yew tree leaves.
- There are also many other analogues and precursors in the Yew Tree's leaves that can be converted into Paclitaxel. Currently these are discarded as waste products.
- Current production is a complicated 13 step process, with methods requiring the use of some hazardous and toxic reagents/solvents.
To solve this, we developed and optimised a pathway that turned an analogue, Xylose Deacetyltaxol (XDT), found at much higher amounts than Baccatin III and 10-DAB, into Paclitaxel. This would not only supplement the supply of Paclitaxel, reducing the need to log the yew trees, but it would also make more efficient use of the tree, increasing the pathways long term sustainability.
Ping Zhu
Ping Zhu’s lab (Peking Union Medical College)
To ensure full usage of the Yew Tree's products, we looked for a biosynthesis pathway that turned other precursors into Paclitaxel. Through our research, we discovered a paper published in nature communications in 2017 by Professor Ping Zhu's lab.(1) This pathway intrigued us because it produced Paclitaxel from a common analogue in the Yew Tree's leaves called XDT, allowing both full usage of the tree and reducing the costs of producing Paclitaxel, as the analogue is cheaper.
We reached out to Professor Ping Zhu, hoping to develop upon the pathway. He was very supportive of the idea to scaffold the enzymes, and we had the opportunity to work closely with his team, gaining knowledge from their experienced understandings of the pathway. A few of their inputs were:
- After having significant problems with expressing a type of β-xylosidase (LXYL-P1-2), we arranged a meeting with Professor Ping Zhu, where he provided us with their most up to date information, recommending expression in a yeast plasmid, rather than traditional E.coli.
- Professor. Zhu helped us identify that the LXYL-P1-2 Spy Tag should be placed at the C-terminus for it to attach properly
Integration
Changes in the design of how we express LXYL:
- We constructed an entirely new yeast plasmid for Xylosidase expression.
- Changed our linker from the N terminus towards the C terminus.
Sharing resources and reaction conditions:
- Helped us figure out the reaction conditions of the pathway, and how to extract Paclitaxel from the pathway. These specifically are; temperature = 37.5ocelsius, pH = 5.5 and time = 15 hours. The specific concentrations of XDT, LXYL, and Acetyl CoA are respecitvely 2mM, o.5mg/mL, and 2mM, and extraction via Ethyl Acetate.
- Through this, we were able to perform our commercialisation work a lot more efficiently, using solid data based around the pathway.
Scaffolding the enzymes could be a very good idea!
Professor Ping Zhu
Yew Tree Environmentalists
Overall Integration into our project execution and design:
We recognised that our Pathway would increase demand for the Yew Tree's leaves, and realised that this would have adverse effects on threatened Yew species such as the Endangered Himalayan Yew. Poorer communities like that in Nepal may exploit natural Himalayan Yews, in order to sell the leaves or bark for extra income.
To proactively address this issue, we worked with communities in the Himalaya, Nepali Academics, Environmentalists, and Botanists to develop a program that teaches sustainable Himalayan Yew farming.
At the centre of this program is a guideline that encourages communities to plant and regenerate the Himalayan Yew due to its biodiversity and cultural significance. This guideline teaches how to farm and harvest the Himalayan Yew without killing it and provides the community with extra income.
The restoration of the Himalayan Yew is one of cultural, environmental, and social significance.
Dr. Prabha Sharma
Why we moved to the next stage
Consideration of Social, Personal, and iGEM values
Maddy McGarvey, a UNSW Arts (Environmental Humanities) and Science (Genetics) student
When running our Education and Public Engagement lecture for Social Science students, we received a thought-provoking question from Maddy.
The question was, "In light of recent climate change protests and talks, I see your project as producing more waste and using more resources. How can you reduce your impact on earth, beyond reducing tree logging?". This stumped us, as we realised it was something that we hadn't thought about previously, propelling us to explore options to reduce the environmental impact of our chemical pathway. Whilst the question spurred our change in thought processes, we realised that it was also a part of our responsibilities. If this pathway was going to be the future of Paclitaxel production, a drug that will be used for many more decades to come, it needed to have as little impact on the environment as possible.
Integration
We also researched more sustainable lab practices, considering how we would eventually impact the environment, and how we could reduce this impact as much as possible.
- We made the shift towards the next iteration in our project - a focus on green chemistry, and chemical engineering to improve our pathway into something that would be better for the world.
- We also looked into better lab practices to further reduce our impacts.
In light of recent climate change protests and talks, I see your project as producing more waste and using more resources. How can you reduce your impact on earth, beyond reducing tree logging?
Ms Maddy McGarvey
Iteration 3: Incorporating Concepts of Green Chemistry
Overview
Green chemistry is a philosophy that was developed to reduce the hazardous nature of chemical processes, so that they are less damaging to the environment. As this field has grown, it has evolved into 12 core principles that holistically address the environmental impact of chemical processes. These principles range from reducing waste, sourcing renewable reagents, designing for energy efficiency, and much more.
In this iteration, we sought to integrate these concepts into our pathway, reducing the environmental impacts of our pathway. This iteration reflected the concerns of the greater public, and prepared our pathway for long term Paclitaxel production. Regarding this, we enlisted the help of the Centre of Green Chemistry Australia (Professor Douglass Macfarlane), and the directors of the Green Chemistry Centre of Excellence in the UK. We worked closely with both centres to integrate green chemistry principles such as a by-product recycling loop and reusing waste products to ensure our pathway would be good for the future of Paclitaxel production.
Douglas Macfarlane
A green chemistry professor at the Australian Centre of Green Chemistry
Douglass introduced us to the 12 principles of Green Chemistry specifically the concept of Atom Economics.
Integration
We applied the concept of Atom Economics, which essentially focuses on maximising the incorporation of all materials used and produced in a process into the final product. We saw by extension, that we could do the same but through incorporating CoA-SH, a by-product of our proposed pathway, into the current semi-synthetic pathway. We worked with Douglass Macfarlane in the implementation of this loop, which will help prevent wastage and improve the overall pathways efficiency.
Kevin skyping with Dr. Douglass Macfarlane
Introducing atom economics, can make your production more sustainable, produce less waste, and also makes it more attractive to investors
Dr. Douglas Macfarlane
Green Chemistry Centre of Excellence Directors
Professor James Clark and Dr. Avtar Matharu
GCCE is an award-winning green chemistry centre at York University. The directors helped implement green chemistry concepts into our project.
Both directors were happy to hear about our project, and confirmed that it indeed was complying with green chemistry principles. Our pathway uses 2 non-toxic solvents/reagents, a large improvement over the 13 hazardous solvents/reagents in the current semi-synthetic pathway.
The directors also helped us ways in which we could move our pathway towards zero waste using their experience.
Kevin, Melissa and Justine skyping with directors Professor James Clark and Dr. Avtar Matharu
- Originally, we looked for methods aimed at preventing Xylose wastage through recycling it to produce Acetyl CoA and funneling back into the production pathway. When we talked with them however, their advice helped us see that this would not comply with concepts of green chemistry. It would add further energy expenditure, more by-products, and wouldn’t be as efficient.
- They also recommended that the biomass waste produced by the pathway could have a-lot of other uses, and should not be discarded, like currently done in industry.
We also asked them about how we could increase our energy efficiencies in the lab. Upon review of our pathway, they noted that this shouldn’t be our main concern. Rather, when upscaling our pathway we should be careful about adding too many processes. However, they did confirm that our pathway was an improvement in terms of energy efficiency compared to the current 13 steps of the semi-synthesis pathway.
Integration
- As recycling Xylose would not be environmentally friendly, we explored other options. We realised, through further consultations with the directors, that Xylose is actually a commonly used product, with a wide variety of uses. There could be value in extracting and reselling the product. As a result of this realisation, we integrated a method into our project for extracting Xylose using Boric Acid. Although this would reduce the green chemistry nature of our project, we could counter this by reducing the waste our pathway would use, and weakening the strength of the boric acid used.
- We explored potential uses for biomass waste produced by Paclitaxel Production. One idea was to extract cellulose from the biomass and use it as an Acetyl donor for our pathway. This meant our pathway could enable full use of the tree. However, as noted by Professor James Clark, we needed to ensure that we weren’t adding complicated and unnecessary steps to achieve this.
- Overall confirmation that our lab design, and project execution so far has been in line with green chemistry principles, and will have a positive impact on the environment.
Your pathway can definitely be classed as a greener alternative to current semi-synthesis.
Professor James Clark
Why we moved to the next stage
UNSW Founders Incubation Program
Nathalie Rafae.
UNSW Founders is an incubation program at UNSW, that we worked closely with to figure out how to commercialise our pathway and our product Assemblase. Assigned to our case was Nathalie Rafae.
Natalie provided valuable insight, aiding in the development of our business plan, and pushing us towards the next iteration of our project.
She reinforced that despite our sustainable or green chemistry integrations, if we wanted to enact positive change, we needed to ensure it would be adopted by Industry.
Nathalie also helped us determine industry contacts and guided our future HP work, maintaining our aim of improving our pathway’s commercial viability.
Kevin and Sebastian meeting Nathalie Rafae
Integration
- We decided to talk to potential buyers, such as Venture Capitalists and Pharmaceutical companies to see what they would like to see in our pathway
- We made the switch towards focusing on improving the commercial viability of the pathway.
To really get things going, startups should be encouraged to develop a healthy dialogue with relevant industries to adopt their emerging technologies and present them as critical elements in achieving a pathway of sustainability, efficiency, and wellbeing
Ms. Nathalie Rafae
Iteration 4: Making the Pathway commercially attractive
Overview
In this stage, we prepared our pathway to be adopted industrially, through consultations with professionals like startup incubators and venture capitalists. Through working with these individuals, we gained advice on what steps to take to ensure the commercial viability of our pathway.
- Through the advice of Peter Grudzinskas, he urged us that we focus on the versatility and commercial strengths of Assemblase itself rather than the pathway. When offering to pharmaceutical companies the option to improve lots of their enzymatic pathways, beyond just Paclitaxel production, will make it more attractive of an investment.
- Finding a cheaper reagent to use as an acetyl donor. This was discovered through continued work with Professor Ping Zhu, and their recommendation that Vinyl Acetate is a cheaper and more abundant reagent that can also act as an acetyl donor.
- Preparing our pathway to be scaled up for industry sized fermentation and bioreactors. Here, we worked with the UNSW Recombinant Products Facility to develop 2 filtration methods for retrieving Assemblase with enzymes attached for re-use, and retrieval of Paclitaxel. These methods are Beaded mobilisation and Tangential Flow Filtration. We applied Molecular Dynamics modelling to figure out the sizes of the filter.
Peter Grudzinskas
Ex-Chief Marketing Officer of Abbot Pharmaceuticals
Peter combined experience and knowledge of the field of pharmaceuticals, as well as marketing. Through our conversations with Peter, we gained future directions that would allow our pathway to be adopted by industry.
Peter recommended that we adjust the focus of our business plan to ensure that we can commercialise both the pathway and Assemblase.
- Whilst it is beneficial to highlight improvements of our Paclitaxel production pathway, it would be more valuable to prioritise the marketing of Assemblase’s versatility. This expands our horizons in terms of funding and industry adoption as the pathway can be applied to many different pharmaceutical companies, beyond those specialising in Paclitaxel production.
Peter also recommended that we gain the opinion of someone who has had scientific experience with positioning products and pathways for commercial success.
Integration
We refocused our commercialisation work towards emphasising not only the pathway, but the flexibility of Assemblase. This made corresponding changes to:
- Our projects purpose, expanding to incorporate both pathways of Paclitaxel production and how we can allow companies to produce Paclitaxel through both methods aided by Assemblase.
- Repurposing our business plan towards the versatility of Assemblase, rather than just our Paclitaxel production pathway.
- Guided our next IHP interaction.
Assemblase is more versatile than your pathway, and would be an easier sell. Focus on providing both to companies, rather than just your alternative pathway.
Mr. Peter Grudzinski
Dr. Alison Todd
Co-founder and Chief Scientific Officer of SpeeDx
Dr Alison Todd is a serial inventor with 18 biotechnology related patents, and the driver of SpeeDx’s commercial success. Her understanding of what it takes to turn ideas into a commercially viable product helped significantly guide us throughout our project.s throughout our project significantly.
Alison helped us realise that although our pathway is great in terms of its potential benefits, companies will not adopt it unless changes were made to the pathways design to fit companies current processes. In particular, she noted that companies will be against the expensive costs of Acetyl Salts as it is not a common reagent. She urged us to look for cheaper alternatives.
Furthermore, she noted that to improve our chances of our pathway being adopted, we would need to prepare it for commercial production up-scaling.
Alison also introduced concepts that would help our projects commercial execution later down the line. Specifically, check whether you have "Freedom to Operate". This means ensuring that none of a project's components infringe upon other patents. We brought up to her that one of the components of our project, the SpyCatcher and SnoopTag system, was patented by researchers in the US. She recommended to obtain a licensing agreement as early as possible.
Kevin and Justine meeting Alison at the SpeedX head office in Sydney.
Integration
Following Alison’s advice, research was done into finding cheaper solvents and reagents for producing Paclitaxel. Working again with Professor Ping Zhu (Above IHP interaction), he recommended that we explore the viability of using Vinyl Acetate as an alternative Acetyl Donor than Acetyl Salts. This would significantly reduce costs of production as the cost of Acetyl Salts is $1500AUD/100mg, whilst Vinyl Acetate costs $25AUD/100mg (Sigma Aldrich). We worked with Alison to gain her insight on our proposed changes, and she noted that this would be dependent on the company we talk to and what they value - cost savings, or green chemistry. Having the two options available will help increase commercial viability of the pathway.
We also attempted to design ways we could scale up our production pathway, and for producing our recombinant proteins. This meant preparing it for use in bioreactors, that is commonly used within industry. This led us to our next IHP interaction, the UNSW Recombinant Products Facility.
Our projects commercial execution would first focus early on obtaining the "Freedom to Operate" to ensure we weren't infringing on any patents.
Definitely look for cheaper reagents, I think that could help a lot.
Dr. Alison Todd
Helene Lebhar
Recombinant Products Facility (RPF) Manager
The Recombinant Products Facility assist in the commercial scale up of protein production and purification projects. Helene, the Facility Manager, helped make our pathway compatible for use in bioreactors and large-scale reaction conditions through the development of a recovery method.
To do this, we needed to figure out how to implement a recovery method for reaction products and conjugated components of Assemblase. This would increase its commercial attractiveness as customers would be able to retrieve and reuse Assemblase.
She recommended that to figure out the size of the filter, we would need to perform modelling work.
Integration
With Helene, we developed 2 applicable recovery methods, each with its own unique use conditions.
- Cross Flow Filtration methods. This recovery method is cheap, and is suitable for early testing and small scale users. To design the filter size, we used Molecular Dynamics simulations to determine the size of Assemblase at its smallest points. (25 nanometres). This meant that the filter size needed to be smaller than 25nm, which would allow for the removal of our product Paclitaxel but retain Assemblase and conjugated enzymes for reuse. We settled on the use of an industry standard 20nm filter which would also reduce costs further.
- Bead Immobilisation methods. This method sees greater commercial viability. It involves fixating Assemblase and conjugated enzymes onto beads and storing it in a column. A solution containing the reagents travel through the column, and react with the enzymes attached to Assemblase and the beads. Due to the low amounts of reagents and steps in our pathway, this method is possible. We used predicted enzyme kinetics values to derive the flow through rate and residence times of products.
Nicole, Kevin, and Melissa at the Recombinant Products Facility
Recovering Assemblase means customers can recycle and reuse the enzymes. I think this not only increases the commercial viability, it's also alot more sustainable.
Ms. Helene Lebhar
Integrated Human Practices Gold Criteria
Does it serve as an inspiring example to others? Convince the judges that your approach to Human Practices reflects iGEM’s values, public interests, and should serve as a model for others.
Our project is a strong reflection of public interests - in fact, our 3rd IHP iteration incorporates green chemistry principles because of social feedback, and the desires to reduce our impact on earth.
We've also shown a consideration of iGEMs values, and the potential impacts of our project, as well as taking a proactive approach towards addressing them. We recognised that if our project would develop into a business, it would increase demand and exploitation of the endangered Himalayan Yew. Through working with the relevant communities and Nepali/Himalaya academics, we've been able to develop an extensive guide that encourages regeneration and sustainable farming of the trees, reducing potential impacts of our project.
We believe this work has only been possible through the implementation of our impactful engineering framework, that takes into account more than just data into the design of our project. We hope that through showing the effectiveness of this framework, and providing it back to the community, will inspire other engineers to do the same.
Was their work well integrated throughout their project? Demonstrate how your project’s purpose, design and/or execution evolved based on findings from your Human Practices work.
Our project has evolved over time by integrating our Human practices (HP) work throughout our project. As we gained new understandings, our projects purpose begun to change and adapt towards a sustainability focus, rather than just cost reductions. We continued to integrate HP work into our project, for instance in how we planned to execute our project. These changes ensured that our pathway was responsible and good for the world, by preventing harmful impacts from occurring. We also integrated HP into the design of our laboratory processes and experiments. For instance, the expression vectors we used, the enzymes we chose, or the recycling systems we used. Overall, by integrating our HP work we have been better able to achieve our goals of sustainable and efficient Paclitaxel production.
Is it documented in a way that others can build upon? Clearly communicate the methods, process and results of your work in your wiki, poster and presentation. If you communicate your HP work elsewhere, tell us where, and why.
We've documented our IHP work in the form of progressive iterations, that we believe not only show the methods and process of our work, but also allows future teams the possibility to build upon these iterations.
We've also clearly communicated this on our poster and at our presentation, as well as in special awards such as Education and Public Engagement or Supporting Entrepreneurship.
Was it thoughtfully implemented? Did they explain the context, rationale, and prior work? Explain why your choose your approach and reference prior work inside and outside iGEM that informed your methods.
The other benefit of using progressive iterations is that it allows us to segregate our work into sections that clearly show a streamlined process of thinking, work, and connects it to previous contexts and realisations.
This approach of progressive iterations also allowed us to zero in on each stage, and focus on new ideas, interactions, and improvements that would help get us to the end goal of that iteration. For example, by focusing on commercialising our pathway and surrounding ourselves with the right information and resources, we were able to achieve our end goals of improving the pathways commercial viability.
Did it incorporate different stakeholder views? Engage with a diversity of views (not just your own and those of your friends!), and tell us your rationale for selecting relevant stakeholders and incorporating any feedback.
People we have talked to:
Relevant individuals in the Himalaya: Adapting our project and guide for use within communities in Nepal and India. Specifically, we talked to Nepali Academics, who were able to relay information back from these communities.
Synthetic Biology Academics: We talked to a variety of Academics who could assist in the design and construction of our scaffold and pathways. This varied from protein experts, to people who have specifically worked with our construct.
Environmentalists and Botanists: We incorporated their advice into our project and guide. This ensured greater prevention of negative impacts of our project.
Green Chemists: To align our project with public values, we worked with 2 different green chemistry centres to help ensure our project would have as little long term environmental impact as possible.
PBS and Government officials: Our projects end users would be the Government, who in Australia negotiate and purchase drugs like Paclitaxel for citizens. We communicated with them to gain their opinion on whether our work was neccessary
Venture Capitalists and Incubator Programs: To ensure our pathway would be able to enact positive change, we needed to prepare our pathway for commercialisation. To do this, we worked with industry professionals who were able to guide us in the right direction.
Cancer Researchers: This helped us understand the importance of Paclitaxel, and whether the work we were doing was needed by society.
Did they convince you that their HP activities helped create a project that is responsible and good for the world? Provide clear documentation and a compelling rationale that you have conducted your work with care and foresight.
We have shown that through our HP activities, we have been able to evolve our project to ensure greater good for the world. This was only possible through taking care and foresight with our work, and considering the potential impacts of our pathway if it were to be fully scaled up.
From creating a program that encourages the sustainable regeneration of the Himalayan Yew, to reducing our projects environmental impacts, HP has been integral in guiding our work towards responsible and positive change.