Understand the problem
Problem overview
When we started our project, what we concerned about were some social and medical issues caused by the wide-spread use and legalization of drugs, like unintentional cannabis ingestion, addiction control of certain crowd and drug abuse, etc.
It is of great sadness that we face the reality: nowadays, more and more people get addicted to drugs contrary to their own willingness. So we determined to deal with this hot issue we concerned about.
Our basic idea is to construct a comprehensive Δ9-THC detection-degradation system targeting all these conditions above. The system is programmed to function as a buffer of the rapid decriminalization process faced with challenges such as unprepared policies, disagreements and intercultural communications by providing the choice to be informed and opt out. While successfully reducing the addiction of cannabis, we expect to provide a secure system for future cannabis exploration so as to broaden the application prospects of cannabis.
Perspective of protection
From the very beginning of the project, we set our sights on three groups that are often overlooked in social life, namely narcotics police passively infected with drug addiction, the certain crowd who may get addicted to cannabis through medical use and those who accidentally become addicted when studying abroad or traveling. Unable to control their addiction through mainstream means, so we finalized our project theme “Cannabis ‘Vaccine’” to provide them with convenient means of protecting themselves. As our project continued to progress, we also found that our idea is of great significance to pregnant women. Given that cannabis ingestion during gestation period is really dangerous, we expect that our project can also provide a choice for mothers-to-be to protect themselves from addiction.
Society's attitude towards science
A synthetic biology solution is an appropriate solution to the present problems. However, we still need some professional suggestions to refine our project as well as further assess our values.
【Professor Sen Li】
This project of BNU-China team is a very interesting idea, which is designed to create a new type of engineered bacteria strain that can reproduce in human intestine and secrete a variety of proteins. These proteins include three enzymes which catalyze the reactions to eliminate Δ9-THC in cannabis and one reporter protein (phycocyanin). According to the design of this project, the engineered strain can sense a trace of Δ9-THC and make quick response. It also possesses the suicide and controlled switches. These designs are quite innovative. The achievement of this project will be helpful in solving the problem of cannabis intake by mistake. It can also be used in prevention of cannabis addiction. Some advice:
(1) This project involves the expression of multiple proteins, so it is necessary to select appropriate protocols to successfully express a variety of proteins.
(2) This project involves the prokaryotic construction and expression of secretory proteins and membrane proteins, so the team should do many experiments to get the best results.
【Professor Ying Zhang】
With the rise of cannabis use in some western countries, problems like many child-bearing couples continue to use it throughout the whole pregnancy might be even worrying. However, fetal and children’s development has been implicated since adverse effects of parental cannabis use on pregnancy established. Besides the impacts on pregnant outcomes, such as retarded embryo development and disrupted embryo implantation, maternal cannabis use was reported to be associated with abnormal in placenta, increased anxiety, intellectual disability and learning disorders in offspring. Paternal cannabis exposure was also related to male fertility and might cause long-lasting effects on neurodevelopmental behavior in offspring. Thus, developing a rapid and efficient method to evaluate individual cannabis consumption will not only be beneficial for pregnancy, but also provide a basis in the guidelines of personalized drug usage. Here, the 2022 BNU-China developed an intestinal colonization bacterium, which could digest Δ9-tetrahydrocannabinol (Δ9-THC) into cannabinoid glucuronic acid and represent blue excrement, opened a new avenue in cannabis consumption detection. We believe that it might also be useful in reducing cannabis harm if work with other intestinal flora, which will be a new idea and direction of cannabis control in the future.
Both of the two professors speak highly of our project, which helps us explore the scope of our human practice and make a difference. Also, when we face difficulties, the professors’ words always come to our mind, making us feel that our work is meaningful and inclusive, thus giving us strength.
Interacting with those affected
We recognized that science serves the good of the people, so we decided to find out what we could do to comprehend society’s concerns and incorporate their opinions into our proposed solution. We believed that a solution must consistently consult stakeholders and integrate their voices, so that a respectful and responsible solution could be developed. Opening conversations with people all around the world greatly informed the initial development of our project. This helped us shape the foundation of our human-centered design.
Questionnaire survey
We designed a detailed questionnaire on related problems to find out whether our values on “social” are appropriate. This questionnaire includes 5 questions we concerned, namely whether the public know the basic knowledge of drugs, whether they are aware of some common circumstances where unintentional ingestion of drugs may happen, how they understand the drug-related law and the drug control policies in China, their attitude towards the medical use of some drugs and whether they find our project do make sense.
To better examine the knowledge of drugs and make it easy for the public to understand the drugs intuitively, we added many illustrations of different drugs. Apart from the basic knowledge, we investigated if they clearly understand the harm of drugs. Also, we explained the classification of drugs. Then, we made a serious of assumptions where unintentional digestion of drugs may happen, and asked people to pick whatever situation they find possible. Further more, we designed some questions to find out how they will react if someone has already taken drugs mistakenly.
Given that the drug-related laws are not the same around the world, we designed two versions of the module of laws. In the Chinese version, we asked three specific questions about the drug-related laws in China. In the oversea version, we asked about their attitude towards the legalization of drugs and we briefly described our idea and asked for a feedback on our cannabis “vaccine”.
The analysis of questionnaire is as follows:
In our sample population (342 people, including both Chinese and foreigners), most people could distinguish between new and traditional drugs. They had a comprehensive understanding of the abnormal manifestations of drug abuse, the characteristics of long-term drug users, and the harm of drug abuse to the body. They had a high vigilance. Most people knew well about the treatment of drug abuse, but about 40% of the people did not know that they should drink a lot of water immediately to promote perspiration and detoxification. At the same time, a small number of people still mistakenly believed that they should hide the truth and not go to the hospital or the police station.
With regard to the specific legal provisions and punishment methods for drug abuse and trafficking, the knowledge popularization rate is not high.
In China, the production and application of cannabis are limited, and cannabis is not widely used in clinical practice. About 30% of the people made a mistake in judging the appearance of cannabis, and about 50% of the people said that they could not distinguish clearly. Only 30% of the people correctly chose the part where cannabis produced the addictive substance Δ9-THC, and about half of them chose "not know much". More than 70% of the population can correctly judge the difference in the content of addictive substances between industrial cannabis and prohibited varieties of cannabis, but no more than 50% of the population could tell the difference in appearance and that both were addictive. More than 90% of the population knew that it was illegal to grow cannabis in China without permission.
More than 60% of the people supported that certain drugs with medical value should be "reasonably used within the scope permitted by law", while more than 30% of the people did not support or thought that "it is better to gradually replace such drugs and finally ban them". Many people were overwhelmed by what to do after eating cannabis by mistake, and it was difficult for minorities to find an effective means of protection. About 80% of the sample population support the use of microorganisms to suppress cannabis addictive substances, so as to better utilize the medical value of cannabis, including the two Australians who participated in the questionnaire.
The result of our questionnaire gives us confidence in the desirability of our project, proving that what we concern is actually what the society needs at present.
Offline science promotion activity
Moreover, we are not satisfied with online communication only. To better let voices and values heard, as well as to give publicity to our project and synthetic biology, we also held a field event in Beijing, the capital of China. First, we wanted to reinforce the students' sense of participation in the activity, so we designed the “Your Quiz on the Block”. We improved the questionnaire distributed to the public in the early stage, retained the objective knowledge questions in the original questionnaire in the content, and added a scoring mechanism in the form, so as to stimulate the interest of the respondents. At the end of the test, respondents will receive feedback in the form of scores and correct answers to all questions. At the same time, we prepared fancy gifts - project brochure (to introduce synthetic biology, iGEM and our project), "cannabis ‘vaccine’" game card (adapted from a board role-playing game called "Werewolf kill", and let the roles associated with our project) and fruit juice drinks. In addition to Chinese college students of our age, we also attracted children, elderly people and people of other different age groups, as well as foreign friends. We asked nuanced questions to draw out how our project could influence these stakeholders.
Some people suggested that after consuming cannabis by mistake, the psychological pressure caused by the addiction of cannabis would be too high, making it difficult for them to face the public opinion, so they may commit suicide. This makes us realize that in our country, it is difficult for groups that mistakenly eat cannabis and other drugs to find an effective way to protect themselves from unintentional drug ingestion and even addiction by avoiding drug discrimination and social public pressure.
The response to our activities has been surprisingly positive and the students were very active to join. Participants signed our posters, and we succeeded in bringing iGEM and our project to a larger audience. Much to our delight, almost all the participants spoke highly of our project and encouraged us to go further in this field and overcome all the difficulties, which really inspired us to endeavor to fulfill our goal.
Hospital Specialist Interview
Since our topic also involves the promotion of cannabis for medical use, we went further to respectfully engage with doctors from primary hospitals, who may also be impacted by our project. In this regard, we interviewed Dr. Shen Yejun, chief physician of neurology and associate professor of Nantong University in Rugao County People's Hospital of Jiangsu Province (Rugao Hospital affiliated to Nantong University), and Dr. Luo Pei, director of cardiovascular medicine, to ask them about the clinical application of cannabis, its extracts in China, and their views on this.
In interviews, both doctors mentioned cannabidiol products. Nowadays, five Chinese companies have already been licensed to produce cannabidiol products, and studies have shown that such cannabis extracts can treat epilepsy, major depression, anxiety, insomnia and even have anti-cancer effects. Both doctors affirmed the medical value of cannabis extracts, however, they also believed that since China is not a country where cannabis is legal, the use of cannabis products was highly controversial in terms of law, ethics and price. In the case that cannabis drugs were not irreplaceable, hospitals and patients would prefer the commonly used traditional medicines. In other words, without significant medical advantages, the scale and frequency of its medical applications be limited.
After that, our team's interviewer showed them 2022 BNU-China's project, and received positive responses like "it is amazing if it can really control addiction", which may help promote the use of cannabis extract related drugs.
In summary, it is necessary and meaningful to solve this problem, which encouraged us to endeavor to fulfill our goal.
Our values
When designing our projects, we chose “social” and “medicine” as our core values. Given that what we concerned about are some social and medical issues related to drugs, such as the unintentional cannabis ingestion and drug abuse in medicine, we designed a detailed questionnaire on related problems and consulted professional doctors to find out whether our values were appropriate.
It turns out that more than 80% of the 342 people from around the world and both of the doctors we interviewed all spoke highly of our values and support the use of synthetic biology to handle the social issues we concern, so as to better utilize the medical value of cannabis, which gives us confidence in the desirability of our project. With the background research mentioned above and our constant reflection throughout the project, we successfully ensure that the values we concerned about are appropriate and the goal we endeavor to fulfill is responsible and good for the world.
Psychological stress
According to our questionnaire covering both domestic and foreign countries, many people are at a loss about what to do after eating cannabis by mistake, and as a minority, it is difficult to find an effective means of protection. Even when communicating with the public about offline publicity projects, some people put forward the idea that the psychological pressure caused by the addiction of cannabis is too high, which makes it difficult for them to face the public opinion, or they even commit suicide. This makes us realize that in our country, it is difficult for groups who take in cannabis and other drugs by mistake to find an effective way to avoid drug discrimination and public pressure to protect themselves from unwitting drug intake and even addiction.
Sense of Responsibility
We believe that whether drug abuse is legal or not, people (including the minority groups that may be ignored) have their rights to know if they have taken in cannabis, rather than passively consuming it against their will. Undoubtedly, our project can effectively solve this problem that is often ignored by the society while maintaining relative privacy. Our team hopes to contribute our strength to the world and be responsible for society and the world through synthetic biology and iGEM.
Ethics
However, at the beginning of the project design, we also realized a very important and difficult problem, which involved ethics. Our engineered bacteria should be verified that it can sense Δ9-THC and express the protein subsquently. However, we could not use Δ9-THC which is considered as the prohibited drug in China and controlled by the Public Security. After consulting the data and communicating with Professor Zhu Xudong and Professor Yang Dong, we made a compromise to use 11-OH-Δ9-THC which can also induce the pathways efficiently. In this way, we can achieve a relatively feasible balance between national laws, public trust, social responsibility and our project completion.
Synthetic biology
Why synthetic biology?
The existing first aid measures for addiction after taking in cannabis by mistake are only those for poisoning symptoms caused by one-time excessive consumption of cannabis, such as vomiting and gastric lavage. However, this method is limited by that the amount of cannabis ingestion needs to meet the standard of poisoning when it has done great harm to the body, and it cannot guarantee whether the amount human body has absorbed before being sent to the hospital for emergency treatment will cause addiction or not.
The scheme we selected can quickly sense the Δ9-THC ingested by the body, and react to express appropriate quantity of required substances for Δ9-THC degradation. In theory, it has little side effects on the body (the specific situation still needs to be combined with the clinical situation). Moreover, our engineered bacteria have a dual suicide mechanism, which can ensure the control of suicide of engineered bacteria.
Why can only be synthetic biology
Our scheme requires a Δ9-THC sensor in the intestine, which enables adjustion of the corresponding substances expression according to the amount of Δ9-THC. If we use a physical device, we can easily imagine the precision and complexity of the device which means that it needs materials with good human compatibility and consideration of how to repair or just choosing a one-time use method. We are not satisfied to just provide the first aid for a minority of people who can afford it, so we design our product. Generally, our team believes that such a scheme can only be achieved through synthetic biology, and only synthetic biology can meet the conditions we require.
A Dialectical Look at the Pros and Cons of Genetic Engineering—Risks and Benefits
Engineered bacteria risk
When carrying out a new project, we should pay great attention to the risks it brings and responsibilities we should take. During communications with professors, we gradually improved our project as follows. Firstly, we chose the probiotic Escherichia coli Nissle 1917 as our chassis which has no bad effect on human body. Secondly, our engineered bacteria take two suicide mechanisms to ensure that the activity of the engineered bacteria is controllable and could not be spread out in the environment.
Other risks
Our team has considered other risks brought about by the project adequately, such as the pubic views of cannabis and our engineering. That’s because if the project is carried out without the public’s approvement, it will bring unexpected public pressure and social conflicts. It means that public's awareness of cannabis will directly affect how our project is fundamentally responsible for society: we hope that people who do not want to be exposed to cannabis addiction can be alerted and with the first aid in time. Thus, we initially designed a questionnaire to know about the public's awareness of cannabis and other drugs, and then we carried out a number of public popular science activities and Charity Class, hoping to provide an opportunity for anyone who wanted to know more about synthetic biology and our project. At the end of the project, we held an offline publicity meeting for human practice activities to popularize the knowledge of cannabis and other drugs to the public and introduce iGEM and synthetic biology. In particular, it introduced how to use synthetic biology to solve the problem of emergent social problems like cannabis addiction, forming a closed loop, which is in line with our expectations.
Design and experimental conception
How HP Affects Our Design
BNU China has been brainstorming nonstop from December 2021 to May 2022, and has produced forty-four interesting topics covering treatment, games, environmental protection, microbial programming, exploration technology innovation and other fields. However, after weighing many factors like the importance, urgency, responsibility, public will learned from questionnaires during human practical activities and laboratory conditions , we have made our direction clearer : the report and first aid for cannabis addiction.
How HP Affects Our Experiments
Human practice activities run through our whole project. At the beginning of the project, we distributed questionnaires to know about the public's awareness of drugs and attitude towards the significance of our project, which made us firm in the way of project implementation. We communicated with doctors about the project prospect and improved the use of engineered bacteria. At each stage of the experiment process, we actively communicated with many excellent teams like Tsinghua and BNUZH-China, which led us to reflect and find loopholes in our project experimental conception and optimize it. For example, other excellent teams pointed out that using only one type of bacteria to express three enzymes would make our bacteria too burdensome, so our team changed to use three types of bacteria to express three enzymes separately after discussion. When we could not successfully purify our proteins, we discussed with Professor Yang and recieved positive feedback and suggestion. When our experiment reached the bottleneck stage, the public's positive feedback and expectation on our project in both online and offline publicity activities made our experimental team members more confident and energetic in repeating and improving the experiment. Human practice has played a significant and positive role in the whole experiment, and it is also the main way for our experimental group to re-engineer, test and connect with the society.
