"Synthetic biology is a relatively new science with tremendous potential to change how we view and know the life science, but like many developing technologies, it has provoked ethical concerns from the scientific community and the public and confronts demands for new regulatory measures". (Prof. Bracha Rager-Zisman, Department of Microbiology Immunology and Genetics, Ben-Gurion University of the Negev) .
Synthetic biology promises significant advances in areas such as biofuels, specialty chemicals, agriculture, and medicine but also poses some potential risks.
Many concerns might stem from the field of synthetic biology. For example modifying an organism for medical purposes or environmental care is still a debate in our culture. The lack of knowledge and the complexity of this field arise many questions and concerns among the general public. Furthermore, similar concerns are expressed by scientists who specialized in other fields of research. We thought that as we modify organisms in our lab enabling them to preform new functions, we should learn our limitations and the complexities are involved in synthetic biology. We aimed to study the bioethical issues that may arise from our project to ensure no harm can be caused by our product.
Shimon Glick describes several ethical issues related to Synthetic Biology from a Jewish aspect in a paper he published a few years ago:” Synthetic Biology: A Jewish View” (1): Ethics raises many issues and controversy in science. According to Judaism philosophy, man is considered as a collaborator with God; his motives to research are pure. His goal is to improve mankind and its surroundings. However, there are many risks when we deal with science, like deliberate abuse or dangerous miscalculations.
Meeting with bioethics experts
During the summer, we met several experts from the bioethics field, who gave us general new ethical insights that might be relevant for our project.
First, we met with Prof. Ute Deichmann, an expert in History and Philosophy of Science. Prof. Deichmann gave us an initial overview of bioethical issues in research. We learned that ethics issues are reviewed and examined as soon as a new scientific method or technology is being developed and becoming useful for different applications. Furthermore, ethic issues might arise during the research process. For instance, researchers confronts ethical questions regarding integrity, objectivity and authenticity during the research process. Therefore, researchers should ask themselves what the motivation that fuels my research is. The researcher's desire for knowledge and achievements should not overcome the obligation for ethical values such as dignity, integrity and candor. Thus, we learned that ethical issues need to be considered in many aspects.
Second, we learned that our designed product is encountered with a relativity new term called genetically modified organism (GMO). GMO is an organism whose genetic material has been altered by genetic engineering techniques. GMO became wildly used to produce genetically modified crops, medications, medical devices and nano-technology. Furthermore, GMOs is widely used in many aspects of scientific research.
We also learned that there are differences in the regulation of GMOs between countries, when a marked difference can be found between the United states that favor for GMO products while Europe union is basically against.
Third, we asked ourselves what is the potentially harmful consequences that may emerge when implementing new technology. Does a genetically modified organism can have a negatively effects on the environment or on human being? Such concerns are also considered a biosafety matter as creating a GMO is accompanied with lots of uncertainties regarding its future effects on the environment. Apart from biosafety, synthetic biology raises also biosecurity concerns, as products of synthetic biology could potentially be used for malicious intentions.
The regulation of bioethical issue in Israel
In recent years, effective biosafety laws and regulations have been adapted by several countries to prevent terrorists and other hostile powers from obtaining dangerous biological agents, technologies, or information that would allow them to develop and manufacture biological weapons.
In 2008, the Israeli parliament ("Kenesset") decided to tighten biosecurity measures and legislated the regulation of research into biological disease agents law, which provides a legislative framework to conduct research involved biological disease agents. The law calls for the establishment of a council to regulate and monitor research on select infectious disease agents. It also prescribes institutional committees with defined responsibilities and identifies means of control, including penalties and liabilities.
Until the beginning of the 50's there were no clear guide lines or standards for ethical behavior in conducting a research. World-wide governments, including the federal regime in the USA, had a minor role in regulating and enforcing ethical standards.
As of today, much progress has been made in the regulation of bioethical issues. The federal government As of today, much progress has been made in the regulation of bioethical issues. The federal government in the USA and the European governments enforce all aspects regarding the research process, implementing rules and regulations. In order to enforce these regulations, government instructed the establishment of the Institutional Review Board (IRB). IRB is an institute that exist in every academic establishment or research institute and function to implement regulations regarding research ethics.
Judaism Bioethical principals
Learning about bioethical issues, we continued to explore the history of bioethics. We met with Prof. Shimon Glick from the Faculty of Health Sciences (Ben-Gurion University of the Negev, Be'er-Sheva, Israel), an expert in the field of Jewish medical ethics. In the meeting Prof. Glick thought us about Jewish views of bioethics. We discussed ethical issues concerning new technology, including synthetic biology.
In his paper, "Synthetic Biology: A Jewish View”, Prof. Glick describes the Jewish approach towards scientific progress as well rounded and aware to the problems it presents: "Judaism traditionally looks favorably on man as a co-creator with God and encourages research for the benefit of humankind. Thus, the Jewish tradition would haves a positive attitude towards the current goals of synthetic biology. But, in the Jewish tradition man is also charged with stewardship over nature and is admonished to preserve and nurture, not just to exploit and destroy".
The Book of Genesis indicates that God gave people control over the animals and earth, while Genesis emphasizes that the role of people is to maintain and take care of the world. The Talmud which is a central text of Rabbinic Judaism, teaches a basic ethical principle in Jewish law, the 'Bal Tashchit' ("do not destroy") commend. The commend orders men not to waste or destroy our earth, the commend is invoked only for destruction that is deemed unnecessary. Many hold the view that pollution is an insult to the creation of the world, and it is considered immoral to put commercial concerns before care for God's creation. However, humans are regarded as having a special place in the created order, and their well-being is paramount. Humans are not seen as just another part of the ecosystem, so moral decisions about environmental issues have to take account of their well-being.
After meeting Prof. Glick, we were eager to learn more about how Judaism deals ethical issues regarding scientific research and progress. We found a quote from Rabi Moshe Ben Maimon (Maimonidas), a philosopher, scientist, polymath and one of the most important adjudicators in the Jewish religion that lived in the Middle Ages :"If men possessed wisdom, which stands in the same relation to the form of man as the sight to the eye, they would not cause any injury to themselves or to others, for the knowledge of the truth removes hatred and quarrels, and prevents mutual injuries". Maimonidas didn’t see any future harm in the search for wisdom as he derived that the search and common goal cancels any violent notion.
Judaism holds an ambivalent opinion regarding genetic engineering and technologic innovation. It indicates the need of finding a balance between the human's wellbeing and preserving the creation. These principals are much alike some aspects in the modern approach towards bioethics.
Ethical concerns regarding the PlastiCure project
Familiarizing with the GMO concept, we discovered that there is a discrepancy between the way the public perceive bioethics and the way it is studied and practiced. Reaching the public in various events, we made an effort to explain the safety precocious we took in order to prevent health and environment hazards. Furthermore, we explained our motivation for working with modified microorganisms to solve the problem of plastic pollution. We realized that measured ethical risks must be taken in our project. Therefore, we designed several approaches to address these risks. For example:
- Bacterium self - destruction switch mechanism that was developed by BGU iGEM Team 2013, And allows to control the life time of the modified organism.
- Enforced symbiosis between our two types of bacteria that do not allow them to survive separately on PET out of our controlled system.
PlastiCure, BGU iGEM team conducted research from pure motives. Our goal was to find plastic waste a solution. One of our main guide lines is to create a safe and controlled work environment. Therefore, we followed strict safety rules that enable us to ensure minimum mistakes and ideal conditions during our work.
Safe Lab Work:
All of our project's lab members received safety training by our advisors, and had to partake in a lab safety online course offered by the Ben Gurion University safety department. In this course, we learned about emergency protocols, safety classification of biological labs, and working with new chemicals. In the lab, we wear protective clothing and gloves at all times (unless working with fire). In necessary cases, we also wore protective glasses and face masks, worked in fume hoods / biological hoods etc. All experiments were done considering all appropriate safety protocols, after consulting our PI and advisors.
In our project, we preformed multiple growth experiments using different intermediates in the PET degradation pathway as carbon sources. Some of the chemicals have specific safety instructions according to their MSDS, which were printed out and stored in the lab for all of the members to read and work according to. (For example, at times, it was necessary to work with a chemical like Catechol, or to handle Ethidium bromide waste, in a fume hood).
Safe Project Design (Safety Risks to the General Public):
Our final goal as the BGU iGEM team is to create an operating biofuel cell, which will break down polyethylene terephthalate (PET) using E. coli and P. putida. We chose to work with these bacteria, as they are known chassis organisms, are easy to manipulate, and are risk group 1 (P. Putida - DSMZ) – they do not cause diseases in human. Moreover, we use the P. putida KT2440 strain, which is the first Gram-negative soil bacterium to be certified as a safety strain by the Recombinant DNA Advisory Committee (Federal Register, 1982(3)) and is the preferred host for cloning and gene expression for Gram-negative soil bacteria (Nelson, K. E., et al. 2002(4)).
With the safety of the environment in mind, we designed a metabolic cascade to degrade the toxic intermediates in the PET degradation pathway, to non-toxic compounds that can be used by the bacterium for energy in the TCA cycle. This way, the degradation process does not release any pollutants or toxins to the environment other than the carbon dioxide and water bacteria produce in their own metabolic processes.
In order to ensure the safety of our product, we integrated into our design the self-destruct mechanism developed by the 2013 Ben Gurion University iGEM team. With this mechanism, not only the expression of our genes will be dependent on an IPTG inducer, but it will also force our E. coli to be fully dependent on an unnatural amino acid (UAA). Without supplying it to the bacteria medium, or in case of release to the environment (which will only happen by accident since we do not intend to release our bacteria), our E. coli bacteria will not survive. Our second bacterium, P. putida, which is design to consume TPA (one of the PET degradation products), would not be able to consume PET as it is dependent on LC-Cutinase (the enzyme which breaks the initial bond in the PET polymer into TPA and EG), since LC-Cutinase is expressed and secreted from E. coli. Therefore, the genetic modification done on this bacterium will be useless, since it is responsible for degrading TPA, which is a commodity chemical that usually does not exist abundantly in nature.
Local Rules and Regulations:
- World Health Organization (WHO) – Laboratory biosafety manual, third edition
- Restrictions on Genetically Modified Organisms: Israel
- IBSA – Israel Biological Safety Association
- Ben Gurion University – Safety Department
- Synthetic biology: a Jewish view. Glick S. Perspectives in Biology and Medicine, Volume 55 (4), 2012, pp. 571-580
- Register, F. (1982). Certified host-vector systems. Washington, DC, 47, 17197.
- (4) Nelson, K. E., Weinel, C., Paulsen, I. T., Dodson, R. J., Hilbert, H., Martins dos Santos, V. A. P., ... & Brinkac, L. (2002). Complete genome sequence and comparative analysis of the metabolically versatile Pseudomonas putida KT2440. Environmental microbiology, 4(12), 799-808.