Team:TECHNION-ISRAEL/HP/Silver
Human Practices
When we first came up with the idea for creating immune tolerance, the reactions in the team were both enthusiastic and concerned. Although the idea had great potential, we thought that iGEM might not be the right place to pursue it, due to time and logistical limitations. In the end, we really connected with the idea and the virtue of tolerance that it represents.
Our original idea was very preliminary, thus in order to understand whether it was realistic we held a meeting with prof. Doron Melamed, director of an Immunology laboratory in the medical faculty of the Technion institution. We also wanted to know if it was feasible test our system within the timeframe of the iGEM competition. Prof. Melamed validated our basic premise, and said he believed it was possible to test our system within the time frame.
We also consulted with other experts in the field of immunology, including: Dr. Ayal Hendel , Dr. Jerry Stein , and Prof. Zila Zuckerman .
Since the experts mostly agreed that our basic assumptions were reasonable, we decided to go for it.
At this point we had to overcome a fundamental difficulty that we faced. How were we to deliver our treatment without eliciting an immune response? After much thought, we came up with the idea of using a “Trojan Horse” strategy in our system. We read about a number of controllable induction methods for mammalian cells and met with Prof. Ben-Zion Levi, director of the Molecular Biotechnology lab. We discussed possible systems and chose a system that is both effective and well characterized – the Tet-Off system.
Other difficulties we faced were how to culture mammalian cells? Which cells should we work with? The laboratory we work with is a synthetic biology laboratory that focuses on bacteria and yeast, and therefore didn't have much experience working with mammalian cells. In order to answer all these questions we met with Prof. Prof. Zila Zuckerman , director of Bone Marrow Transplantation in Rambam hospital. We presented our project to her and she advised us on how to genetically engineer HSCs, how to grow them and in general, how to work with them in the laboratory.
From the beginning, we understood our project would necessitate treating babies who lack immunological memory. As we progressed in our project we discovered, based on surveys and expert opinions, that this raised many safety, and ethical, issues. What would happen if an allergy to the drug develops? Is it ethical to subject healthy babies to a gene therapy when there is a possibility they may have never gotten sick? Is it feasible that such a treatment will ever be approved by the FDA? And many more. We decided to contend each problem separately, and this led to many fascinating and unexpected developments within our project.
For more information regarding these developments, please see our Integrated HP page.
Additionally, we wanted to figure out how our treatment would interact with the real world. How would it be manufactured? What are the most appropriate tools currently on the market? And what would be required to achieve FDA approval?
To this end, we consulted Dr. Ayal Hendel, from Bar Ilan University, who directs a lab currently researching similar gene therapies in babies using cord blood. Dr. Hendel generously invited us to visit his lab and learn about how they engineer HSCs from cord blood.
We learned that the process is efficient, but complex so we searched for new devices that might be able to automate the procedure. We discovered that a new medical device by the name “CliniMacs Prodigy” is able to separate the CD34+ HSCs from the cord blood, electroporate our gene of interest into the cells and culture them, all within a closed, fully automated system. We contacted the provider in Israel and asked for information regarding its cost and capabilities. They explained that the device can run many programs and is capable of executing what we require. The basic cost per machine is $250,000, while additional costs for setup and user training varied.
We were thrilled to discover that the technology necessary to execute our treatment already existed, but we still needed to investigate the rules and regulations regarding FDA approval.
Although it was clear to us that actually bringing a new drug to market would not be possible within the iGEM, we thoroughly researched the FDA guidelines so we could change our experiments and protocols in accordance. Read more about these changes in our Integrated HP page.
From the very beginning we searched for a way to prove our project works. Animal testing was ruled out early on as it is discouraged in iGEM, and the timeframe did not allow for an ethics permit. Thus, we looked for an alternative way to test our theory in-vitro. We designed not one, but two separate assays to test our system: the B cell assay and the T cells assay . As both these assays required displaying antibodies on non-immune mammalian cells, a very difficult task, we consulted with Prof. Yoram Reiter an expert in the field of synthetic immunology. With his help we were able to design our final assay constructs.
Lastly, during meetings with experts and interactions with the community , many ethical issues came up. As such we decided to reach out to Prof. Laurens Landeweerd, a world renowned bioethicist from the University of Radboud. Prof. Landeweerd was kind enough to meet with us over skype and discuss our project. While preparing for this meeting, we discovered how complex ethics is, and how difficult it is for scientists lacking a philosophy background to effectively consider ethical issues. We lacked both experience and resources. Our Conversation with Prof. Landeweerd was enlightening and only convinced us further of the need for ethics resources within iGEM.
In addition to meeting with experts related to the scientific aspects of the project, we wanted to consult professionals regarding the best way to engage the public. For this purpose, we met with Associate Professor Ayelet Baram - Tsabari - Dean of the the Faculty of Scientific Education. Ayelet is an expert in the field of science communication, and her advice was valuable in helping us organize our various community activities. Check out our work HERE .
Last, we participated in a conference on "Communication in Science", which included lectures, artistic performances, and discussions with leading science communication researchers. Participation in the conference was a very interesting and instructive experience for us, helping us better understand how to communicate our science to the public.
We believe that human practice is an integral part of iGEM and as such, it was integral of our project. We set out to discover how our project could be integrated into the real world and what affect that would have, and discovered far more than we could have ever expected. These discoveries lead to some of the best elements within our project.
Department of Biotechnology & Food Engineering
Technion – Israel Institute of Technology
Haifa 32000, Israel
igem.technion.2017@gmail.com
