International Genetically Engineered Machine Foundation
by IGEM (International Genetically Engineered Machine Foundation
The International Genetically Engineered Machine (iGEM) Foundation is dedicated to education and competition, advancement of synthetic biology, and the development of open community and collaboration. In 2012, iGEM spun out of MIT and became an independent nonprofit organization located in Cambridge, Massachusetts, USA. The iGEM Foundation fosters scientific research and education through organizing and operating the iGEM Competition, the premier student synthetic biology competition. It also fosters scientific research and education by establishing and operating the Registry of Standard Biological Parts, a community collection of biological components. The organization promotes the advancement of science and education by developing an open community of students and practitioners in schools, laboratories, research institutes, and industry. The iGEM community has a long history of involving students and the public in the development of the new field of synthetic biology.
iGEM 2014 Platinum Partners
iGEM 2014 Partners
iGEM 2014 Gold-Level Sponsors
iGEM 2014 Silver-Level Sponsors
What is the iGEM Competition?
The International Genetically Engineered Machine competition (iGEM) is the premiere undergraduate Synthetic Biology competition. Student teams are given a kit of biological parts at the beginning of the summer from the Registry of Standard Biological Parts. Working at their own schools over the summer, they use these parts and new parts of their own design to build biological systems and operate them in living cells. This project design and competition format is an exceptionally motivating and effective teaching method. In 2011 iGEM expanded to include a High School Division and an Entrepreneurship Division in 2012.
SAFETY
i
GEM takes safety seriously and we continue to update our procedures and protocols every year. In 2013, we have created several levels of safety forms that must be completed by the teams depending on what type of organisms and parts they are working with. More information, instruction and the download links to the forms can be found on the iGEM 2013 safety page.
Intro
According to the WHO biosafety is the prevention of unintentional exposure to pathogens and toxins, or their accidental release, whereas biosecurity is the prevention of loss, theft, misuse, diversion or intentional release of pathogens and toxins.
1) Identifying safety issues in your project:
The factors of interest in a risk assessment dealing with biological material include: pathogenicity, route of transmission, agent stability, infectious dose, concentration, origin of the potentially infectious material, availability of information, availability of an effective prophylaxis, availability of medical surveillance, experience and skill level of at-risk personnel. Your iGEM project is usually working with a non-infectious host organism (Biosafety level 1 or 2) so you may concentrate more on the engineered parts, devices and systems.
From an engineering and scientific point of view, risk assessment deals with the probability that a certain hazard is going to happen. In risk assessment: Risk = probability x hazard
[[NOTE: NO WAY TO POSSIBLY DETERMINE THE FOLLOWING AS PRODUCTS ARE UNIQUE, NEVER EXISTED BEFORE, THUS NO STUDIES ON THEM! - DNI]]
Probability:
- Could there be an unplanned event or series of events involving your project, resulting in either death, injury, occupational illness, damage to equipment or property, or damage to the environment? How likely is that going to happen?
- Does your project require the exposure or release of the engineered organism to people or the environment (e.g. as medicine, for bioremediation)?
Hazard:
- Could your device, when working properly, represent a hazard to people or the environment?
- Is your engineered organism infectious? Does it produce a toxic product? Does it interfere with human physiology or the environment?
- What would happen if one or several bioparts change their function or stop working as intended (e.g. through mutation)? How would the whole device or system change its properties and what unintended effects would result thereof?
- What unintended effects could you foresee after your engineered organism is released to the environment?
- Try to think outside the box, what is the absolute worst case scenario for human health or the environment, that you could imagine?
Risks need to be seen in conjunction with the benefits. Although we would like to decrease the risk to absolute zero, this is hardly possible. So the question is not so much if something is safe or not, but rather if it is safe enough! Deciding whether a risk is acceptable or safe enough is no easy task and people may have different opinions. A whole professional field, so called risk management deals with that issue.
2) Documentation and management of safety issues
Datasheets on registered biobricks already contain some but few information on safety. For example, reliability of parts is be included, distinguishing genetic reliability and performance reliability that describe the number of generations it takes to cripple 50% of the circuits in the cells. This is a first step towards a more comprehensive safety characterization of biological circuits, but more detailed safety characterizations will be necessary to do a proper risk assessment to decide whether or not a device is safe enough for your particular application. Your contributions to documenting safety issues in parts, devices and systems are therefore greatly appreciated!
Here are some examples how you could document your work:
- Parts: Most bioparts will not pose any safety problems, but some can. The simplest example would be a part that encodes for a toxic protein (e.g. Botox, botulinum toxin, or ricin WIKI link). Other parts may produce milder toxins or anaphylatoxins (causing allergic reactions in some people). The fact that a protein can be toxic doesn't automatically mean that you cannot use it, some proteins are helpful pharmaceuticals in lower doses but become toxic in higher doses. In general the safety categorization of parts would best be based on the conventional BSL 1 to 4 levels and Select Agents and Toxins list (see e.g. the HHS AND USDA Select Agents AND TOXINS list https://www.selectagents.gov/Select%20Agents%20and%20Toxins%20List.html).
- Devices and systems: a genetic circuit could exhibit different safety characteristics than the parts it is based upon. Thus different safety categories should also be used for devices and systems.
- Cell chassis enhancement: Parts that extend the environmental range of a cell chassis, by increasing for example the tolerance of relevant biotic and abiotic conditions, should be documented as well.
Other questions are: How can a safety issue be reported that was discovered in a certain bio-circuit and that was not foreseen (emergent) so other people can learn from that experience? How can safety and security aspects be integrated into the design process so the design software automatically informs the designer in case the newly designed circuit exhibits certain safety problems?
3) Playing by the rules:
There is already a number of international and national guidelines, laws and professional associations that you have to consider. Here is an overview of some of them:
[[long list of international and national documents]]
4) Other ideas
4.1. Biosafety engineering
Synthetic biology holds the potential to make biology not only easier to engineer but also safer to engineer. In many established engineering disciplines (e.g. mechanical engineering, aviation, space flight, electronics, software) safety engineering is already an established subset of systems engineering. (System) safety engineering is an engineering discipline that employs specialized professional knowledge and skills in applying scientific and engineering principles, criteria, and techniques to identify and eliminate hazards, in order to reduce the associated risks. Safety engineering assures that a system doesn't pose a risk even when parts of it fail. This is more than needed in synthetic biology due to the evolutionary forces of biological systems. If synthetic biology is going to become the new systems engineering of biology, then it needs to establish an equivalent subset in safety engineering: biosafety engineering (Schmidt 2009).
Biosafety engineering could be practiced by designing robust genetic circuits that account for possible failure of single parts or subsystems, but still keep working or at least don't cause any harm to human health or the environment. Safety engineering has many techniques to design safer circuits (systems), for example
- Event Tree Analysis and
- Fault Tree Analysis
Both methods are normally used in assessing the safety of engineering systems (e.g. aircraft, space travel, mechanical engineering, nuclear energy) based on standardized parts and true engineering designs.
In a device or system, for example, a mutation in one of the bioparts could cause the part to become dysfunctional. The Event Tree Analysis (ETA) would look at the way the whole system is going to be affected by the failed part. It will answer the questions: Will the device or system still be able to fulfill its tasks? Will it behave in a different way, and if yes in which way? Or will it shut down completely? Based on this analysis additional safety systems could be installed, such as redundant sub-circuits.
The Fault Tree Analysis (FTA), on the other hand, looks at defined unwanted failures of the systems and then traces backward to the necessary and sufficient causes. For example, a genetic circuit should not fail in a way that leads to the overproduction of a particular protein that is regulated by the network. The FTA can show which basic events could cause such an overproduction, and thus help to improve the circuit to avoid these unwanted failure, for example in designing the circuit in a way that all basic events would cause the expression of the protein to diminish but never to increase.
The full range of possibilities to include safety considerations in designing biological circuits has not yet been explored in great detail but will be extremely helpful. How could you contribute to make it happen?
[Note: In their own words, synthetic biology = genetic engineering on steroids -- and notechnology = synthetic biology on steroids! One has to wonder what steroids these people are hooked on. The fact that these engineers see no differences between complex interacting and mutating living organic biological systems and simple mechanical standard parts says it all. Alert: There are NO SUCH THINGS AS STANDARD PARTS in a living organic biological system!, truly mindboggling! Note that totally unique and novel engineered organisms are involved, and therefore there exist no previous studies re the real or possible hazards -- or risks or benefits -- they present!!! Not to mention that risk/benefit analysis refers only to utilitarian (probably BIOethics) kinds of ethics! Note that these experiments are being performed by high school and college students around the world [e.g., https://igem.org/Team_List?year=2014] -- and also probably by not a few terrorists around the world Note too that sponsors include MIT and Monsanto. How could so many people NOT have their heads screwed on right (if at all)? Since when do mechanical engineers have the academic credentials to determine anything whatsoever about living organic biological systems??? Most of them have never even taken a single course in biology -- much less in genetics -- much less in human genetics. Even scientists with degrees in any of the multitude of life sciences per se take quite different courses for their degrees (and almost none take courses in engineering or physics -- or in medicine (and vice versa)!). Life does not consist in nor is defined by standard parts or machines! How does this happen??? Even the best and most experienced bus mechanics in downtown Manhattan are not allowed to do brain or cardiac surgery on living human patients in hospitals! Nor are surgeons allowed to build or do mechanical maintenance on buses! Nor are mathematicians credentialed to deliver babies, nor pediatricians credentialed to build elevators. Anybody home?? The article first appeared here.-- DNI]