Human Practice

YiYe-China iGEM’s 2024 project, the early diagnosis of gastric cancer, integrates expert knowledge and addresses the public’s needs and vision for gastric cancer diagnosis at an early development stage. Gastric cancer is also known as stomach cancer. It is the fifth leading cancer in terms of both diagnostic figures and cancer-related deaths. Astonished by the data and inspired by the current study of the correlation between G3BP1 protein and gastric cancer, we developed a new diagnosis method, using G3BP1 protein and HSU mRNA to construct a plasmid as a biomarker.

Our commitment to Human Practices (HP) centers on critically evaluating the ethical and global impact of our synthetic biology project. We have focused on improving accessibility to cervical cancer diagnosis and advancing women’s health worldwide. Insights from the public, industry experts, and cervical cancer specialists have guided our project and product enhancement. Below, we present a comprehensive record of our HP interactions.

Our interest in gastric cancer (GC) stems from a video one of our team members learned that their favorite content creator was diagnosed with late-stage GC due to unhealthy eating habits and the lack of timely medical check-ups. When we heard about this story, we were all shocked and wanted to do something.

Upon further research, we learned that GC is the world’s fifth-largest cancer, and that timely diagnosis can significantly increase the survival rate of GC patients. This made us wonder if we could develop a piece of technology to diagnose GC at early stages so that more GC patients can receive timely treatment and live longer and healthier lives.

To genuinely understand the need of the public, we designed a questionnaire about GC and shared it online. In our questionnaire, we asked questions regarding their own experiences with GC, their understanding of cancer, and their life habits. To guarantee that the respondents are focused on the survey, we added a question that says, “Please choose false for this question.”, in order to reduce errors. Subsequently, we received 90 valid responses from all ages and genders. Here, we provide some of the key figures.

As shown in Figure 1, 23.33% of the respondents responded that at least one person around them has experienced GC. This made us deeply sorry and more determined to use our own efforts to improve the situation. Seldom cases responded that over four people around had been diagnosed with GC.

As shown in Figure 2, approximately 30% of the people we studied didn’t receive regular health checks at least once a year, as the WHO recommends. As many people are reluctant to take medical check-ups actively, we want to design a simple yet accurate method to diagnose GC.

Afterward, as shown in Figure 3, more than half of the respondents claimed that they preferred endoscopy over PET-CT and biomarker testing. Thus, we wanted to design a test based on endoscopy so that most people would like to take the test.

During the summer holiday, many of our team members visited the offices of Kindstar Global Gene Technology, where Director Hao gave us a tour. Kindstar Global plays a leading role in the Chinese gene testing field and provides esoteric testing services and technologies to hospitals to develop advanced and accurate testing to help develop personalized treatment for patients. During the visit, we learned how the biotesting industry works and how hospitals collaborate with firms in order to improve efficiency.

After we decided to work on the early diagnosis of GC and participate in the iGEM competition, we started to raise funds on social platforms including WeChat, QQ, Weibo, and Xiaohongshu. Currently, we have raised more than 700 CNY, as shown in Figure 4. We have used some of this money to purchase the experimental equipment and reagents we need and print the leaflets we designed for science popularization. By the end of the project, we will donate the rest of the money to the Chinese Red Cross to support patients suffering from GC.

In the course of developing our project, we placed a strong emphasis on ensuring that our product and work process is responsible and beneficial to the world, thereby adhering to our core values. This was achieved by being open-minded and constantly refining our understanding, design, and actions by engaging in constructive interviews with experts in the field—researchers, doctors, and stakeholders who frequently challenged our ideas and guided us toward making our project safer, scientifically accurate, and ethically sound. During those processes, we realized the importance of raising social awareness and commercializing our design.

During the visit to Kindstar Global, we interviewed Mr. Hao Wei, the director of the company. At that time, we were progressing our experiments and interested in the future application of our testing method to the market. Thus, we prepared several questions about the commercialization of a new testing method. Mr. Hao serves as a director in the Kindstar Global group.

He told us that it is not simple to commercialize a diagnosis method. The basic protocol of commercialization is to certify a biomarker, analyze clinical data, develop a mature diagnosis method, and industrialization. Firstly, we should ensure our biomarker is efficient. This requires vast article reading and computer simulation. Next, we should collaborate with doctors, collect clinical samples, and transition the research method from qualitative observation to quantitative analysis. He suggested the use of digital PCR. Additionally, he stressed the significance of the stability of the testing method.

Mr. Hao highlighted the importance of collaboration with medical services. The collaboration requires trust between both sides. Hospitals require accuracy and efficiency, while firms require quality and integrity of the samples.

During the COVID-19 pandemic, we were firm with COVID-19 nucleic acid testing. However, the results were not always accurate, and the cases of fake negatives and fake positives. How could our method decrease those fake outcomes? Mr. Hao introduced us to the definition of “grey area.” A grey area is the interval that appears between the sure negatives and sure positives. Data in this area cannot be defined as “negative” or “positive”. More testing methods are required to prove the result mutually. Even though we can still not reduce those biases completely. Because those biases could have made serious impacts on clinical cases, we should still be cautious and keep on improving our method.

Meanwhile, Mr. Hao has analyzed the current situation of the Chinese gene testing industry. As a newly developed and rising industry, we have several advantages and disadvantages. China has its natural advantage as a populated country, thus providing various samples for many kinds of diseases, even rare ones. Nonetheless, how to raise people’s awareness and improve our testing technology is still a problem we should consider.

As Neil Armstrong claimed, “A small step of a man, a giant leap of mankind.” Perhaps we are on the opposite; our effort only plays a tiny role in the biological history of mankind, yet we are starting our voyage as biologists who may rewrite history and change the world.

Afterward, we visited Doctor Tong Qiang at Wuhan University People’s Hospital and asked him about the future trends in GC diagnosis.

Doctor Tong was concerned about the current situation of GC in China. Firstly, the diet and lifestyle in China have an obvious correlation with GC, in the case of the high levels of fat, sugar, and salt intake. Those habits could significantly lead to GC. Secondly, the medical system of China has some drawbacks in the face of the situation. The patients in China who are diagnosed with GC have always been termed to be in the second or third stage, which is difficult to cure. This revealed the problem of early diagnosis.

Doctor Tong suggested we solve the problem from the two factors above.

As for the first problem, we should not only diagnose GC but also prevent GC. If people all followed a healthier diet, the GC diagnosis rate should have decreased. We have to raise people’s awareness of keeping on a healthy diet. With the control of fat, sugar, and salt, we can have a promising future in controlling GC.

The solution to the second problem requires two-sided efforts. On the first hand, we should improve our project by decreasing the cost and increasing the efficiency. By decreasing the cost, we can significantly reduce the burden on individuals and the government, thus promoting the method better; on the other hand, we should put efforts into pursuing the government. “The Japanese government is advanced in this case,” he claimed, “they provide residents with two free regular GC checks a year, and this is what we should learn.” This reminds us about our duty to social progress. We should make an effort to encourage our government to reform the current medical insurance system and provide free regular GC tests. Yet, the effort of decreasing the cost and increasing the efficiency must be completed before this, to prepare for a large-scale application.

At last, he expressed his good wishes. He said that our program was the same as us, we were the promising force who could become the game-changer in our fight against GC.

As one of the most advanced hospitals in Central China, Wuhan Union Hospital has its fame in the field of cancer treatment. Thus, we went to the Wuhan Union Hospital and interviewed Deputy Director Cheng Yifeng from the Gastrointestinal Department, which has firm experience in GC diagnosis and treatment.

During the interview, he laid out an attractive theory combined with Traditional Chinese Medicine and modern Cancer theory. He claimed that cancer is mainly caused by irritants. “Everyone has oncogene in their body,” he said, “but why some were diagnosed with cancer yet some weren’t?” He laid out some data as an example. Data showed that Henan Province, China, has the highest rate of esophagus cancer. The reason, he claimed to be the unhealthy habit that they stick to boiled water. Boiled water irritated their esophagus too much, thus making them cancer.

In this case, he suggested that keeping on a healthy diet is not only about reducing salt, fat, and sugar but also not intake of too many irritants, including boiled water. This has something to do with the deep change in the health idea of Chinese people. Chinese people are firm in drinking hot water (sometimes even nearly boiled water). This is partly because of the tea culture, which was generated over a thousand years ago. For instance, the recommended temperature for making Chinese Red Tea is 90 degrees Celsius (approximately 194 degrees Fahrenheit), while for Chinese Green Tea, it is 80 degrees Celsius (approximately 176 degrees Fahrenheit), which are both highly above the WHO recommended 20~50 degrees Celsius (approximately 68~122 degrees Fahrenheit).

On the other side, the Chinese government recommended citizens boil water in the 1950s to reduce the bacteria in the water. However, a huge amount of people mistook the boiled water for boiled water, thinking that drinking water at a high temperature can be expected to be healthier.

Despite Boiled water, spicy food was also a significant irritant. The tradition of eating spicy food is also termed a tradition in southern western China, like Chongqing, Sichuan, and also, Wuhan.

Knowing this, we improved our community promotion. We talked more about our traditions, which could be harmful to our health, and recommended a healthier diet and lifestyle (especially the way of drinking water).

Doctor Cheng was also interested in the method we use to collect samples from gastric in our design. He said that our method requires improvement. The most difficult part of the current methods, such as EUS, is to examine patients’ gastric with a flexible tube inside. Although our improvement appeared at the next step, to increase the accuracy of diagnosis, the main disadvantage of EUS hasn’t been improved. The collecting method is still the traditional method, which remains difficult and fails to release the pain of the patients, which is the main reason that prevented patients from receiving regular checks currently. Thus, in the following progress, we should put efforts into working out a new method to take out samples.

Besides, Doctor Cheng also praised our effort in developing a gene testing method. He claimed that gene testing is usually used in an inferior, assistant stage in current cancer treatment in China, which helps doctors to decide what medicine the patient should take. Our effort is to introduce gene testing as a main diagnosis solution, which is revolutionary and may change the era. Yet, we face many difficulties in releasing a new method due to the current stability of the current method. However, We should keep working on strengthening our method’s advantages----high accuracy, low cost, and less pain. Once the world sees and recognizes the advantage of our method which makes it significantly different from the current methods, we will receive success.

While interviewing the previous doctors and having conversations with several patients, we revealed that in cases of cancers, which are considered to be highly fatal diseases, the importance of mental health is the same as physical health care. For the patients at the terminal, mental care aimed to save their souls or to get them well prepared for their last trip perhaps has a more significant meaning. Meanwhile, as a critical illness, cancer makes the patients’ families suffer a lot, even medical workers, including doctors and nurses, will suffer a lot of negative emotional impacts.

Therefore, we invited Doctor Feng Kun from the School of Clinical Medicine and Yuquan Hospital at Tsinghua University. Dr. Feng is a leading expert in psychology and psychosis treatment in China. The purpose of the interview is to figure out the impact on patients with cancer, their families, and medical care workers. Furthermore, we are expected to comprehend the current situation of the mental care system of cancer patients in China and what is the best way to accompany them on their last trip.

Dr. Feng first analyzed the psychological status of patients who suffered from cancer. She claimed that the solution to this question is complex due to the differences that appeared in the category of cancer they suffered (for instance, patients with thyroid tumors are likely to be less anxious due to its harmlessness), the stage they were diagnosed (patients who diagnosed with cancer at the 0 stage or I stage are more likely to be cured), and factors of themselves and their families.

Generally, patients tend to be suspicious when diagnosed with tumors at the very first, even though the truth sometimes appears to be clear; they even seek to deny the truth for comfort. Most of them will choose to do more examinations to ensure the result. Those are more typical in China because of the extreme taboo of disease and death in the Chinese traditional culture. They won’t have a positive attitude towards treatment before breaking the fantasy. In this case, the first challenge the doctors met was to help the patients accept the identities of cancer patients.

In addition, psychological problems not only cause mental diseases like emotional disorders but also impact patients’ physical health, causing irregular dietary habits and sleep disorders. Thus, psychological care plays an identical role in the following treatment process, which can comfort the patients and their families and provoke their motivation to persist.

Nonetheless, the current situation terms to be unsatisfying in China. Dr. Feng claimed that mental health care in cancer treatment has been on the edge for a long time, as there here are only 0.0002875 psychologists per 10 people in China, which is significantly less than those in major developed countries. Among these psychologists, most of them are dealing with mental diseases like major depressive disorder (MDD), thus further less effort can be put into the mental care for cancer patients. To deal with this situation, Dr. Feng emphasized on improvement of the community working system. With more trained community workers, the disadvantages of the shortage of psychologists are likely to be reduced. Furthermore, Dr. Feng suggested a staging system in the mental health care of cancer patients, which provides patients with different evaluation methods, based on the development of tumors.

These all support the significant meaning of our work. With an earlier diagnosis, patients can have a broader choice for treatment, which could increase their sense of hope and reduce the pressure on their families.

For the next topic, we talked about some tragedies when patients and their families have to accept the reality that it’s time to say goodbye. Dr. Feng laid out an example of one of her closest friends, also a psychologist, who was suddenly diagnosed with late-stage pancreatic cancer in the year of 49. When facing death, she performed leisurely and elegantly. She wrote down all her knowledge and thoughts during her lifetime and opened them to the public, alongside several letters to her son to read in different stages of his life. She said, calmly and satisfied, “It is satisfying to say goodbye because I’ve left the best things behind me. I’ve spent my pleasure last two years with my family and I will have plenty of time to do things I like to do in paradise.”

Dr. Feng highlighted that the paramount affair of hospice care is to give love to patients. Families are not wise to avoid the truth and pretend to be placid. Otherwise, they will feel nothing but regrets when a sudden separation comes. It’s recommended to have an honest ceremony during the last time, with families gathering together and expressing their strong feelings of love. “When I think about the case of death, I feel fearless. Because I know the value I left on the world. We have always passed on something from our ancestors, and this is how our civilization passed on. Death is only a part of our life, and once our memories are passed on, we will still be alive.” Dr. Feng said when talking about death.

The last topic is about mental health care for medical workers. According to Dr. Feng, healthcare workers, especially doctors, are also likely to suffer from mental problems. Doctors are usually bearing more stress than other careers due to the professions required and the heavy burden on them. However, mental health care for them is nearly ignored in China. “In this case, doctors are likely to rely on their experience to separate emotions from professions, to support themselves.”

After the interview with Doctor Feng, we’ve gained a bright new version of our effort. During the in-lab work, we mainly focus on the experiments, the data, the molecular, the equipment, or the plasmids, we’ve almost lost the awareness of what we are actually doing. Nonetheless, when we looked into the hearts of patients, their families, and doctors psychologically, we discovered that what we do matters even more than we previously thought. Our purpose isn’t to construct a plasmid or to develop a diagnosis method but to change the lives of thousands of patients. If they had received in-time checks, there could have been fewer tragedies. We could hardly discover the meaning at this level unless we switch the way we observe---- from searching databases and analyzing experimental results to looking into the hearts of individuals. Feel the pain they felt, taste the bitterness of life they have suffered. Although a rational mind is important for biologists and doctors, it is also important for empathy. Sometimes, using commonsense, not scientific analysis, can better touch the true meaning and the initial purpose we are working on.

After interviewing the professionals, we realized the importance of commercializing our design. In the process of commercialization, one of the most important things is to apply for intellectual property protection (IPR).

We’ve studied the market circumstances and the IPR laws, finding that applying for a US patent is a wise choice for our design. On the one hand, the US has a highly developed market in the field of biotechnology and gene technology, which benefits us for the future development of our program; on the other hand, the US has a perfect law system and Law enforcement system in the IPR. In addition, as the contract government of the Paris Convention for the Protection of Industrial Property, the US government can provide patent appliers with international protections and benefits, which further encourages our program’s development with a global vision.

After setting out the plan, we studied US laws (35 USC 112, etc.) in depth and decided to apply for a provisional patent. The provisional patent could reduce our current cost and, expectedly, protect our design so that we can put more effort into working on the details. Additionally, the provisional patent provides international stage protection as well as a formal patent. Through the interview, we have learned that the first step is to perform a patent search. We searched the keywords of our design on databases such as PubMed, Google Scholar, etc, and made clear that our design has its originality in the USA. Next, we worked on preparing the materials for the application form, including a piece of documentary evidence that stands for the non-profit stage of our program according to US law. Currently, we are working on the details of the essays, and in the near future, we will receive our first patent in our lifetime. This will be a remarkable moment for us all.