Synthetic biology can be identified with plentiful scientific advancements: working to improve the treatment of major diseases, stopping the spread of harmful algae blooms in natural bodies of water, and increasing the efficiency of essential genomes. However, such advancements do not come without potential ethical dilemmas. General concerns that apply to many lab settings impact synthetic biology work too. Worries about the safety of lab settings and issues revolving around intellectual property and its fair distribution are a few to mention. Specific concerns that relate this biology work include: playing the role of a higher power, blurring the boundaries between machine and natural life, and abusing the knowledge gained through this line of work. As scientists working to modify the natural or normal functions of living organisms, it is possible to see this as work reminiscent of God’s work during the seven days of creation. Because the work does not seek to create, synthetic biology seeks to mimic God in a qualitative and reverent manner. The modification of living things to encourage certain behavior does appear similar to the work of mechanical engineers developing their machines. Yet, many of the organisms being transformed are historically disregarded in terms of moral status and still operate along the lines of their original functions. Finally, the issue of misused knowledge to hurt rather than heal with this technology is a problem subjective to the scientist at work. As a team of students focused on improving the issues of the world, we will work tirelessly to employ rather than abuse the knowledge at our fingertips.
The ethical issues often brought up for collagen revolve around collagen food supplements. Since much of the commercial collagen, for food and for medicine, are produced from animal sources. Similar to the ethical issues driving veganism, it is reasoned that it is cruel to harm animals. Since our work is aiming to get away from this source of collagen, it would not be a concern for our project.
Our project work combines the work of synthetic biology with the medical benefits of collagen. The work of our team focuses on manufacturing a collagen scaffold for medical use. This goal avoids the ethical concerns of playing god, as we seek not to create but to enhance. Furthermore, we source our collagen from non-animal sources so there is no harm to living creatures. Our E.Coli work to express certain genes; this is natural in E.Coli so it can be construed as forcing nature into machinery. Overall, our team worked hard to address the potential ethical concerns and alleviate any issues before conducting our research.
To bring Collatrix to the public, we researched existing federal policies that would be applicable to the project It would be categorized under Code of Federal Regulations Title 21 as a HCT/Ps (Human cells, tissues, or cellular or tissue-based products). These include products that contain human cells or tissues and intended for human implantation use. As an HCT/Ps, Collatrix would have to undergo 510(k) clearance and premarket approval under the Public Health Service Act. It must be submitted to the FDA to demonstrate that it is safe and effective.
To ensure the quality and safety of our product, we referenced the FDA’s standards for HCT/Ps, which under part 1271, outlines the Current Good Tissue Practice, detailing the methods, and steps including manufacturing, the facilities used, processing, packaging, and distribution of our collagen products.This showed us that we should adhere to safe laboratory practices and continue education for lab members about the risk of contaminants and pathogens.
While doing so, our team made sure to reference patents so our product would be unique and new to the market. While the market currently has a few different collagen products with similar ideas like the adhesive tissue repair patch and collagen sheets (20100233246), the processes used to produce Collatrix are unique and independent from these existing patented ideas.
Currently, there are a few companies that use collagen or hydrogel scaffolds for tissue bioengineering. For example, one company uses 3D bioprinting of collagen to rebuild parts of the human heart [1]. Another company creates hydrogel scaffolds that can be perfused with living cells to create tissues [2]. Due to the high need for collagen, type 1 collagen can be obtained from bovine tissue at a low cost [3]. Currently, these companies do not have a product that can customize polymer properties.
At the moment, the price of printing living tissue varies. Depending on the level of specialization, 3D printers can cost from $1,000 to $100,000 [4]. These printers are associated with additional costs, such as bioinks (costing hundreds of dollars) and skiller operators working for 10 weeks per organ. Other forms of tissue bioengineering involve using bovine connective tissue. Type I collagen can be obtained at $10/mg [3]. At a very small scale, our project costs $500 to build a bioreactor. Overall, our method of using bacteria allows for easier production of high quality collagen. It allows us to harness existing biological pathways to tune a scaffold for specialized cell growth, and this concept does not currently exist in the market.
Because the end goal of our project is to use the expressed Scl2 protein to create a hydrogel to place in someone's knee or elbow, it is important to assess the risks involved with putting our experimental hydrogel in a human. To ensure our hydrogel wouldn’t result in any allergic reaction or rejection when placed in a human, it would have to first be animal tested and then tested once more in a clinical trial setting to confirm it is safe and can be placed inside a human. The majority of clinical trials involving hydrogels pertain to tissue engineering research so it is likely that our hydrogel could move towards clinical trials once it has been successfully tested on animals. Once our project cycled through clinical trials and was deemed safe we could begin placing our hydrogels in joints of willing patients. As for the materials used in our project the only concern in the lab is the Streptococcus pyogenes used which had a risk assessment level of 2 and potentially could cause strep throat. However due to standard safety measures in the lab this issue is easily avoidable. Furthermore, the E. Coli used in the has a risk assessment level of 1 and with standard lab safety it poses no cause for concern. As for product development, the only risk associated with building the bioreactor is related to proper electrical hazards which is easily avoidable when proper safety measures are followed.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045879/
- https://www.joshboughton.com/post/collagen-making-the-ethical-choice
- https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=1271.3
- https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=1271.150
- https://www.fda.gov/vaccines-blood-biologics/tissue-tissue-products
- https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products
- https://www.fda.gov/medical-devices/products-and-medical-procedures/3d-printing-medical-device
- https://pubmed-ncbi-nlm-nih-gov.proxy.library.cornell.edu/31371612/
- https://3dprinting.com/company/3d-systems/industry-collaboration-highlights-path-to-3d-printed- lungs/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702075/#R113
- https://www.sciencedirect.com/science/article/pii/S2405886618300265
- Bioreactor: https://dechema.de/dechema_media/Downloads/Positionspapiere/SingleUse_Microbial_ezl+2Ed+Sept2019.pdf
- Clinical Trial numbers for hydrogels https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237140/
- Streptococcus pyogenes used-https://www.atcc.org/products/baa-595