Team:BNU-China/Human Practices

Introduction

HP Flowchart

Goal Setting

• The severity of obesity in China

• Project preliminary goal setting

Project Refinement with HP

Back to the Public

Achievements

Introduction

In the project, we attempt to define impacts of the obesity on people health in China, and propose our solutions to make our voice heard by the society. Following the guidance of iGEM for Human Practices, we focus on issues that can help us improve our research project and make it more interesting to the society. By interview with people from different fields, conducting market analysis and questionnaire survey we refined our design and continued to improve the project as it developed.

HP Flowchart

Goal Setting

The severity of obesity in China

Gang Lin, director of the Bureau of Public Health of Dongcheng District in Beijing

 

Why did we approach him?

Obesity has been drawing increasing attention from the public in China. The issue has been discussed over and over again on social media and we ourselves have seen people around us grow obese. But how severe is the problem? To get an answer to this question, we paid a visit to Gang Lin, director of the Bureau of Public Health of Dongcheng District in Beijing.

What did we learn?

During the interview we learned that as the leading district of Beijing in the collection of data of residents’ health, Dongcheng District has been dedicating to the task for the past decade. Statistics provided by him clearly demonstrated that there has been a tendency of increase in BMI, especially in the past 4 years, nearing a leap of 20 percent in 2018 (Fig. 1). And we learned that several degrees of obesity severity were classified by BMI and should be dealt with respectively. Only till it develop into a disease should we treat it with medical means. These findings helped us to focus our project. to early stages of obesity disease.

Fig.1 Obesity and overweight rates.
Overweight: BMI 24~28; Obesity: BMI>28

When we discussed causes for the increase in the obesity rate, director Lin told us that statistically, several factors could be implicated, yet few had been confirmed scientifically with solidity. Lin also pointed out that although data collected from Dongcheng was representative to residents in Beijing, it was not so for the whole country, for there is quite big a difference between more and less developed areas in China, both in the obesity rate and its causes. For the reasons above, Lin suggested that we looked up for more information released by national databases.

 

 

BMI Investigation

 

Fig.2 The proportion of people with different BMI

In order to collect real-time data about BMI of people across the country, we conducted a questionnaire. As shown in Fig.2, overweight (BMI 24~27, Chinese standard) and obese (BMI>27, Chinese standard) people account for a large proportion, adding up to more than 30％. Although there is a little difference between data we analyzed and published by government, probably due to sample size, the great threat to health caused by overweight and obesity cannot be ignored.

Contrary to the reality, in the questionnaire the ideal BMI values that people prefer are mostly below 24, which means people in China prefer healthy slender figures, especially women (Fig. 3). Our data also indicate that people in rural area generally have better subjective tolerance in higher BMI, which enlightens us to dig deeper in our later investigation.

Fig.3 Preferred BMI of the public

 

 

 

Project preliminary goal setting

Having learned about the severity of obesity in China, we proposed to find a solution using synthetic biological means. Through early investigation, we decided to make use of intestinal microbes,which could serve as a continuously working biofactory, to produce acetic acid,as it had been reported acetic acid can promote consumption of human white fat tissue.A kill switch was included to prevent contamination the environment outside human body.

Project Refinement with HP

Prof. Yonggong Zhai, specialized in intestinal microbe

 

Why did we approach him?

With the very basic idea formed, we visited a few experts to get feedback on our design. Prof. Yonggong Zhai has been studying intestinal microbe for years and achieved great accomplishment. We asked him for professional suggestions, which would help us to improve our design.

What did we learn?

Prof. Zhai enriched our understanding of the relation between intestinal microbe and human health by analyzing all kinds of findings in recent years. By comparing these results, he concluded that the relation between intestinal microbe and human health was far more complex than some researcher had reviewed. Therefore, many claims should be treated with caution. What’s more, there are so many factors from human body affecting intestinal microbiome and vice versa that discoveries based on model animals could hardly be applied to human, so that the basis of our project had to be solid enough to build upon. He also pointed out that a contamination-proof kill switch alone was not enough to ensure safety, and that the users had to be able to terminate the engineered bacteria once it entered human body. In the end, Prof. Zhai kindly provided us with some data of human intestine activity which could serve as parameters for our design, especially the gastric and intestinal emptying times which are fundamentally taken into use throughout our project design.

How did we refine our project?

We looked for more literatures, and gathered enough evidence to verify the feasibility of our project. We also added a new induced suicide part to specifically eliminate the engineered microbe in the intestine at any time we want. This suicide part is harmless to human body or other native microbe and can be activated by the direct in-taking of an inducer.

★ Return visit

Later with more literature to support our idea we revisited Prof. Zhai and told him about our newly designed induced suicide part, he showed approval for our refinement and gave us his best wishes.

 

 

Prof. Youhe Gao from Peking Union Medical College and BNU

Why did we approach him？

Prof. Gao was a lecturer at Harvard Medical School from 1997 to 2001, and has been a professor of pathophysiology at Peking Union Medical College since 2001. Hence, we wanted to learn more from him about how doctors deal with adiposis and whether our product could be used in medicine.

What did we learn?

During the visit, professor Gao provided us with a more detailed perspective of applications of our project in the future. From him we learned about how a prescription is usually made, that there is always a trade-off between following the standard guidebook and specifying in each case, and that not only potential users, but also doctors, who give advice to patients, are important stakeholders of a new therapy. These suggestions were of great importance to our later investigations.

How did we refine our project?

We added a new plan to interview doctors to figure out whether they are willing to promote our product to patients in the future, which was carried out and played a vital role in our project later.

To refine our project to be more in line with demands of the potential stakeholders, including doctors, patients, and people caring about obesity issue, we carried out our investigation from various aspects. It was these investigations that helped us design our circuit and optimize experiments.

 

 

Doctor Wang, from Hospital of Xiamen University

Why did we approach her?

Doctors have practical experience and specialized knowledge, which means their advice and acceptance are of great importance to us. Whether they are willing to use our products determines our potential market.

What did we learn?

The preliminary version of our project specially focused on the consumption of fat in human body. Thus, only an acetic acid overproduction pathway was included as a means to alleviate obesity. However, when we interviewed Doctor Wang from Hospital of Xiamen University, she expressed her concern in pH changes caused by acetic acid inside the digestive tract and the inactivation of digestive enzymes by this change.

How did we refine our project?

It was only after we successfully increased the production of acetic acid to a remarkable extend did we began to seriously consider the pH issue. As shown in Fig. 3, through titration we found that it takes 11.4% more NaOH to naturalize an acetate-overproducing culture compared to the control culture. This finding urged us to find a solution to this acidification problem.

Fig.4 Acetate production tested by titration

 

 

Interviewing with people caring about obesity issue

Why did we approach them?

As the target customers, people who care about obesity issues might purchase our product in the future, so it is significant to learn their requirements and expectations.

What did we learn?

By interviewing with them, we found that their efforts to lose weight largely rely on drugs. Although healthier approaches were recommended, many of them had neither time to do enough exercise, nor perseverance to stick to a low-calorie diet. These people were fascinated to learn that our bacteria could promote consumption of white fat tissue, but also advised us on finding a solution to reduce absorbance of energy in food, which is achieved by some of them by taking pills. Among these weight losing drugs, the most frequently used is orlistat, which is marked as the most harmless diet pill. Still, it was no pleasant experience, for orlistat functions by inhibiting lipases secreted into the intestine, leaving undigested fat inside the digestive track. Extra fat in the intestine did bother the users a lot.

How did we refine our project?

An additional pathwaythat reduces absorbance of extra energy was included into our circuit. Moreover, to avoid digestive problems caused by acidification, a regulatory module is introduced to inhibit acetate overproduction during digestion.

 

 

Jinxiang Drug Store

Why did we approach them?

Introduced by people caring about obesity issues, we wondered about mechanisms of diet pills on sale, which diet pills are most popular, as well as advantages and drawbacks of weight-losing products.

What did we learn?

Following the lead of people caring obesity issue, we visited Jinxiang Drug Store, where we learned more about different diet drugs. Mr. Li, a clerk at Jinxiang Drug Store, briefed us on different types of diet pills. Li confirmed that as the only qualified OTC drug, orlistat was the most frequently purchased diet pill. Other drugs, although used sometimes with prescription, generally cause harms to human body. As is shown in picture, there were only two OTC drugs in the drug store for customers to choose from, and one of which was a non-medicine healthcare product. All of this means our product has a great potential market.

 

 

Patients

From our visit to the hospital, we got to know one certain patient. It was not obesity but the effort to lose weight that sent her to hospital. Unsatisfied with her figure, she bought and used diet pills from an unqualified merchant. The pills not only took her extra weight, but also her fertility. Other cases are also reported from time to time, where people who blindly seek leanness take unqualified drugs get harmed, some end up with temporary organ failure, others with even less fortune.

What did we learn?

From Jinxiang drug store and patients around us, we found these incidences have gone far beyond our project but to the extent of a social problem. Our findings suggest that people should seek ways to treat obesity reasonably, neither to ignore it, nor to go to the other extreme.

How did we refine our project?

We put more efforts into ensuring there are no side effects of our product, by means of consulting experts and searching literatures.

 

 

★ Return visit to those stakeholders

After having made these refinements, we interviewed the stakeholders once again. The patients were looking forward to being provided one day with an option to reduce weight without so many side effects. Doctor Wang also agreed that considering the fluxion of matter inside intestine, such a design could avoid the interference of digestive enzymes, and that the idea of having bacteria consume extra fat might be feasible. Still, she expressed her concern that as an introduced strain, the engineered bacteria could have trouble in coexisting with native microbes while not disturbing the microbes inside the intestine.

How did we refine our project?

In answer to that problem, we proposed to include an additional colonization module, which enhanced proliferation of the engineered bacteria while confining their maximum density, winning doctor Wang’s approval in the end.

Back to the Public

Analyzing data from State Statistics Bureau

Why did we conduct the analysis?

After the visit to the Bureau of Public Health of Dongcheng District, following the advice from director Lin, we acquired and analyzed years of data from national database, which contains statistics collected from all over the country by the government. By calculating fat content in national food consumption, we figured out per capita fat intake.

Fig.4 Per captia fat intake in China over years

What did we learn?

As is shown in Fig. 4, people gradually preferred food with high fat content in recent years, which makes the module of beta oxidation pathway of fatty acid introduced in our engineered bacteria more significant.

Furthermore, through these works, we found an upsetting trend, that although lagged far behind by urban residents decades ago, the obesity rates of rural residents are experiencing a rapid growth and could exceed those of urban residents in the near future.

 

 

Conducting questionnaire

Why did we conduct the survey?

Shocked by the finding, we carried out our own investigation. By releasing, collecting and analyzing carefully designed questionnaires, we reached following conclusions.

What did we learn?

By comparing groups of people with different BMI (Fig. 5), we found that respondents with high BMI prefer food with high fat content, such as meat and oil-rich spicy food, which means overweight and obesity may be caused by fat intake. Furthermore, respondents with higher BMI showed more interest in our product, which means we can expect a vast market.

We also made a comparison between rural and urban residents (Fig. 6). First, by analyzing diet composition, an increase in fat consumption was relevant to the obesity rate growth statistically. Second, respondents in rural area generally have an unhealthier dietary pattern with obviously more meat and oil. From these observations we proposed that the rapidly growing obesity rate of rural residents might be due to an improvement in the financial condition, due to economic development in those areas, and a health conception failing to evolve as fast.

This consumption was evidenced by our field investigation in Handan of Hebei Province, where it was still considered slight overweight a symbol of better living condition. Meanwhile, a traditional concept is still lasting that the elder generation wishes their children to be a little overweight, which in their mind represents health. Leaving these factors unchanged, it would be only a matter of time that obesity become more and more serious a problem in China.

Fig. 5 Results divided by BMI
Fig. 6 Results divided by area

 

When it comes to the frequency of buying probiotic products, over half of people continually purchase them for multiple reasons, to which they usually afford less than 50 yuan once a time. Approximately 80 percent of respondents believe that there are live bacteria in probiotic products, and they will have effects on our gut flora. All these results indicate that our product has potential to take a place in market.

 

 

Promoting our product

Why did we act?

According to our earlier survey, we found that people in rural areas were facing more severe problems caused by overweight and obesity, accompanied with concepts adverse to health. We strived to better promote our project, as well as more advanced health conceptions, to the population, which we believe is in need of a solution to obesity and advanced scientific ideas about health and bodyweight.

What did we do?

We sent our team members to the countryside near Beijing to tell them about the synthetic biology, intestinal microbe, as well as health problems obesity can cause. We promoted our project as a solution to these issues, and furthermore, to convince them to living a healthier life so as to prevent a large proportion of obesity incidence from happening in the first place.

Although the reality was disconcerting, there was hope as well, for at the end of our trip of promotion, we were happy to find our audience showing a promising attitude towards our concepts, and towards a healthier lifestyle, especially the young.

 

 

Investigations into probiotics products

Why did we conduct this research?

As the topic of intestinal microbiome came into the sight of the public, an increasing number of probiotic products have been developed and released to the market. Many of such products claim that they can promote general health by optimizing the composition of intestinal microbiome. But regardless of the authenticity of this “optimization”, can these products change intestinal microbiome at all?

 

 

Fig. 7 Numbers of alive probiotics in each product

What did we do?

We conducted an investigation on the most popular probiotic products (named A, B, C by us) in the market. In our experiment to test effects of gastric acid on those products, we treated these products with medium containing hydrochloric acid at pH of 2 (close to gastric acid) for one hour and a half (close to the gastric emptying time).

What did we learn?

It has been reported that a large daily intake of live cells (109CFU/day) over a period of time (about 14 days) is required for probiotic effects. However, after the treatment of the hydrochloric acid the live cell numbers of these probiotic products are far below this standard.

Although the cell numbers in the products do agreed to the claimed number, all of them dropped by nearly 4 orders of magnitude after the treatment, revealing an unauthenticity in their advertisements.

Fig. 8 Probiotics density of different products and their endurance to acidic environment

How did we refine our project?

This experiment reminded us of the importance to protect our engineered microbe from gastric acid. Hence, we proposed to use microencapsulation embedding technology in product packaging, and living cells in our product should be over 109 CFU.

Here we document all our human practices activities to remind us, that beyond the “pure science” in the laboratory, the society is where our projects come into life. And in the society lies problem that cannot be solved through science alone, but calls for joined efforts from all over the society.

Achievements

Silver

  • We interviewed director Gang Lin from the Bureau of Public Health and learnt that the overweight and obesity rate has a worrying increase, which solidified our background.
  • After validating the severity of the problem by investigation on BMI of people in China, we determined to alleviate this trend of increasing overweight and obesity in societies.
  • We visited Jinxiang Drug Store to learn more about frequently used diet pills, not only their advantages, but also drawbacks.
  • Communication with patients disturbed by obesity, especially the one who lost fertility due to taking unqualified medicine for weight losing, enlightened us to spread the idea of treating weight scientifically, and to avoid side effects of our product.
  • Attempting to convincing the public into living a healthier life, particularly in less developed areas, we promoted synthetic biology, intestinal microbe, our product and concepts to people in rural areas, with expectation to prevent a large proportion of obesity incidence from happening in the first place.

 

 

Gold

  • Advised by Prof. Yonggong Zhai, we strengthened the theoretical basis of our project, and added a new induced suicide part to specifically eliminate the engineered microbe in the intestine at any time we want.
  • Speaking of therapeutics, Prof. Youhe Gao reminded us of paying more attention to doctors’ attitude, which was conducted afterwards.
  • Inspired by Prof. Gao, we had a conversation with Doctor Wang from Hospital of Xiamen University, who pointed out pH changed by acetate production would influence growth of native intestinal microbe, proved by our optimized titration experiments.
  • People who cared about obesity issue shared their experience in reducing weight with us, enlightened us to manipulate the bacteria to consume lipids inside human intestine. Considering the pH influence, between the β-oxidation pathway and the already-existing acetate overproduction pathway we put a bilateral switch under the control of a digestive sensor.
  • When we paid a return visit to these stakeholders, Doctor Wang expressed concern about the stability of the intestinal microecology. So, we proposed to include an additional colonization module, which enhanced proliferation of the engineered bacteria while confining their maximum density.
  • To get back to the public, we analyzed data from the State Statistics Bureau, conducted questionnaire to whole society, and did a research on probiotic products on the market. In this process, we proposed to use microencapsulation embedding technology in product packaging. Furthermore, we understood the necessity of removing barriers between science and society.

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