Human Practices

Ecological impacts

Taxol is an cytotoxic drug that has immense potential. Unfortunately, getting taxol is not so easy. Its history has been racked with environmental concerns and supply issues that delay Phase I, II, and III clinical trials. Because of the nature of the illness this disease targets--cancer is fatal and many people are willing to spend immense amounts of money for just marginal impacts--time is quite sensitive.[6] An initial Phase II trial at Johns Hopkins University found an activity rate of 30% of taxol against ovarian cancer, [2] and later reports showed 20-50% activity, mostly partial remission [6.] Ovarian cancer results in the death of 12500 women in the US per year, so these results generated strong interest. [6] Taxol was also found to have activity in a variety of other cancers: breast, non-small cell lung, pancreatic, and AIDS-related Kaposi sarcoma. [1] Despite the strong results and urgent need, it took 30 years for taxol to get from nature to being prescribed in clinics. [10] The two main barriers preventing taxol from reaching its full capabilities are supply, as well as safety of its administration.

The Pacific Yew Tree

Taxol was originally isolated from the bark of Pacific Yew tree in 1962 by botanist Arthur Barclay. [1] Pacific Yews are found in Washington and Oregon, slow growing, and not abundant enough to keep up with clinical trial demands. [2] 20,000 pounds of bark--equalling two to four thousand trees--makes 1 kg of taxol.[2] There is about 100 mg of taxol per kg dried bark. This is enough to do in vitro testing, but amounts on the magnitude of grams are needed for tests to officiate taxol as a drug candidate. [3] Not only are yields low from trees, the process of collecting takes time, from waiting to collect in the spring and summer months when park peels easily, to the more than nine months for drying, extraction and recrystallization process. [6] Furthermore, harvesting bark will cause the tree to die, so the process is ecologically expensive. [1] There are many possible solutions to the the supply problem, including producing semisynthetic compounds and isolating taxol derivatives from other parts of the tree. However, each of these methods come with their own barriers.

The active ingredient in Pacific Yew trees is paclitaxel; about three mature trees are needed for one patient. One method discovered to circumvent harvesting Yew bark from the fragile Pacific tree species was harvesting docetaxel from the more common European Yew, Taux Baccata. [11] As a drug, docetaxel is newer, semisynthetic. Taxol can also be synthesized from this precursor in a four step process. [2] Though the ecological cost of docetaxel, it brings much higher rates of negative side effects, including hematologic toxicity and neurotoxicity. [8] There are also economic costs which are further explored in the (**Marketability tab?**) Another potential is plant tissue culture; however, taxol has 11 chiral centers and its biosynthetic pathway is difficult to define. [6] Natural molecules in general are very complex, however as drugs they tend to have less contaminants and toxic side effects compared to chemotherapy, and don’t hurt healthy cells of the patient as much. [15] Total synthesis of taxol was produced by the Nicolaou and Holton groups, but the process was too long to be of commercial value. [3] Instead, the discovery of the pathway may be more useful in manipulating genes that affect enzyme activity involved in biosynthesis. This pathway can be transferred into a biofactory, such as E. Coli, a rapidly growing bacterium, which is what our team aims to tackle.

Sources:

Human Practices

At iGEM we believe societal considerations should be upfront and integrated throughout the design and execution of synthetic biology projects. “Human Practices” refers to iGEM teams’ efforts to actively consider how the world affects their work and the work affects the world. Through your Human Practices activities, your team should demonstrate how you have thought carefully and creatively about whether your project is responsible and good for the world. We invite you to explore issues relating (but not limited) to the ethics, safety, security, and sustainability of your project, and to show how this exploration feeds back into your project purpose, design and execution.

For more information, please see the Human Practices Hub. There you will find:

• an introduction to Human Practices at iGEM
• tips on how to succeed including explanations of judging criteria and advice about how to conduct and document your Human Practices work
• descriptions of exemplary work to inspire you
• links to helpful resources
• And more!

On this page, your team should document all of your Human Practices work and activities. You should write about the Human Practices topics you considered in your project, document any activities you conducted to explore these topics (such as engaging with experts and stakeholders), describe why you took a particular approach (including referencing any work you built upon), and explain if and how you integrated takeaways from your Human Practices work back into your project purpose, design and/or execution.

If your team has gone above and beyond in work related to safety, then you should document this work on your Safety wiki page and provide a description and link on this page. If your team has developed education and public engagement efforts that go beyond a focus on your particular project, and for which would like to nominate your team for the Best Education and Public Engagement Special Prize, you should document this work on your Education and Education wiki page and provide a description and link here.

Silver Medal Criterion #3

Convince the judges you have thought carefully and creatively about whether your work is responsible and good for the world. Document how you have investigated these issues and engaged with your relevant communities, why you chose this approach, and what you have learned. Please note that surveys will not fulfill this criteria unless you follow scientifically valid methods.

Gold Medal Criterion #1

Expand on your silver medal activity by demonstrating how you have integrated the investigated issues into the purpose, design and/or execution of your project. Document how your project has changed based upon your human practices work.

Best Integrated Human Practices Special Prize

To compete for the Best Integrated Human Practices prize, please describe your work on this page and also fill out the description on the judging form.

How does your project affect society and how does society influence the direction of your project? How might ethical considerations and stakeholder input guide your project purpose and design and the experiments you conduct in the lab? How does this feedback enter into the process of your work all through the iGEM competition? Document a thoughtful and creative approach to exploring these questions and how your project evolved in the process to compete for this award!

You must also delete the message box on the top of this page to be eligible for this prize.