Human Practices
"Human Practices is the study of how your work affects the world, and how the world affects your work." — Peter Carr, Director of Judging
1. Introduction
Myelodysplastic Syndromes (MDS) is uncommon before age 50, and the risk increases as a person gets older. It is most commonly diagnosed in people in their 70s. The number of new cases diagnosed each year is likely increasing as the average age of the population increases. After getting a thorough knowledge of the MDS in China, we knew that there are no widely recommended tests to screen for MDS at this time. Through human practices, we sought advices from experts to gain deeper understanding of the demands of our projects and to help us think how to improve our project.
2. Public Survey Data Analysis
Figure 1 the poster of the questionnaire about our project
Through a public survey (Figure1), we engaged with many people in from the world to assess the public's understanding of the early detection and Diagnosis of MDS. Thus, we did online survey, cooperated with another team, and preached our project.
From this survey, we found that only a few people knew the common signs and symptoms in the early stages of MDS. A total of 252 people were interviewed for this questionnaire through the Internet. Most of the interviewers were under the age of 18 or 30-50 years old (Figure2).
Figure 2 the data about the age distribution
Figure 3 the data about if people ever heard of MDS
There are 96.83% of the people from Asian. Half of the 252 individuals had no knowledge of MDS at all, and only close to 8% knew or were very aware of MDS. Most of the 8% of the people learned about MDS from newspapers/magazines or from the people around them (Figure3).
Surprisingly, about 90% of people are unaware of the symptoms of MDS, the diagnostic techniques, and the cost of MDS diagnosis (Figure4). According to the survey, the top three factors that people care about testing are the side effects of the test, the cost of the test, and the accuracy of the test. In the end, half were very confident in our research (Figure5).
Figure 4 the diagnostic technology you know for MDS
Figure 5 people's opinion about our project
This survey was distributed across communities in different cities in China, such as Jinan, Chengdu, Wuhan, Guangzhou. Our team gained a better understanding of the mission and foundation of our project by conducting interviews and analyzing the distributed surveys.
3. Visiting and Learning
3.1. Visit to the Optical Valley BioCity
Four of our team members visited the Optical Valley BioCity. Since Optical Valley BioCity was established in 2007, the biotechnology industry has developed at a compound annual growth rate of 30%. By the end of 2017, Biocity has achieved total industrial revenue of more than 100 billion yuan and more than 1200 enterprises. We were all shocked by the development speed of biological enterprises. In the biotechnology research platform, we visited the cell sorting and analysis laboratory, high-throughput screening laboratory, sequencing laboratory, basic biochemical laboratory, protein purification laboratory, chromatography, spectroscopy laboratory, metabolomics laboratory, and proteomics laboratory.
Figure 6 Group photo of our team members at BioCity in Wuhan
Our close contact with the advanced experimental instruments has added more to our yearning for future research as we further realized the proximity between our project and the activities in the industry. In the Optical Valley Bio-City Innovation Achievements Exhibition and Trading Hall, we also found that the Bio-City is divided into various professional areas and realized the diversification of biotechnology development. Subsequently, we visited the products of multiple enterprises and began to understand the value and application scope of these biotech products and the third-party support provided by BioCity to improve the efficiency of transforming cutting-edge biological research results into products. Finally, we experienced the body fat detector and other products supported by biotechnology.
This visit to the Optical Valley Biological City is a process of sharing how biotechnology moves from small-batch testing in the laboratory to the factory for mass production, thus changing human life. It also makes us understand that biotechnology can create a better future for humankind.
3.2. Visit to the Kindstar Global
In the summer, we went to the Kindstar Global, a large high-end esoteric testing service provider in China, is committed to leading the progress of esoteric testing technologies and services in China and promoting the development and improvement of specialized diagnosis and treatment as well as personalized medicine.
Figure 7 Our team members is visiting the company
Through this visit, we learned more about the importance of our project. We also recognized the current shortcomings of the technology of MDS and the need to improve it before it can enter the real market through conversations with the director of the company.
Figure 8 The director of Kindstar Global giving us a tour around their company
At the end of this visiting, we had a deep interview with Mr. Hao, the Director of Kindstar Global.
Integrated Human Practices
Through human practices, we not only conducted surveys and visited the high-end esoteric testing service provider in China, but also interviewed doctors and interview with the head of the company. Prior to finalizing our project idea, we performed in depth research about how our project is needed in the industry. Thus, our research included hosting multiple interviews with professionals within the medical field.
1. Interview with Mr. Hao
After listening our presentation about the MDS, Dr.Hao told us that MDS is a malignant disease of clonal hematopoiesis, and its incidence is usually covert. Unlike a viral infection, obvious dominant symptoms of MDS occur within 2-3 days. Currently, many detection methods are divided into cell morphology detection, subdivided into an increased proportion of primitive cells and abnormal cell development; Cytogenetic testing; Flow cytometry (FCM); and Molecular genetic testing. The total testing cost is about 10000 yuan ($1400). Under this circumstance, it is a huge expense for an average family. Mr. Hao noted that the number of MDS patients in Kindstar Global generally increases annually. However, this data does not exclude many external factors. For example, the company has expanded outward year by year, and the larger scale makes Kindstar Global accept more patient samples.
Figure 9 Interview with Mr. Hao
During this interview, we have a deeper understanding of the current market situation about MDS testing.Nowadays the detections of MDS are expensive, and this disease is not easy to be found early. Moreover, the laboratory facilities like Kindstar Global services for clinicians all over China, the cost of MDS diagnosis is still prohibitive for most patients coming from third and second-class hospitals all over the country, even in some local hospitals. We gained insight into how development in technologies to make the detection of MDS cost less and more convenient, and it could be proved to be generally applicable in the future days.
We have a belief in our project!
2. Interview with Dr. Xue and Dr. Sun
In this summer, we met Dr. Xue and Dr. Sun. Firstly, we discussed what MDS is and its symptoms. However, MDS is sometimes found when a person sees a doctor because of signs or symptoms they are having. These signs and symptoms often do not show up in the early stages of MDS. For another reason, the examination cost of MDS is very expensive as Mr. Hao has said before. Thus, we need to find another more affordable way to examine MDS.
Studies indicated that aberrant splicing is strongly associated with MDS. According to research, there are many RNA splicing-related genes, such as SF3B1, U2AF2, and SRSF2, which have been found to have mutations in around 50% of MDS patients. In our project, we design a plasmid sensor to examine the dysregulation of RNA splicing. After knowing the principle of our experiment, we exchanged ideas with the doctors.
Figure 10 Interview with Dr. Xue and Dr. Sun
This interview with Dr. Xue and Dr. Sun not only let us know how medical therapy works and the limitations of MDS diagnosis, but also gave some suggestions on our methods. The doctor pointed out that aberrant splicing is not the only cause of MDS, so our examination may not as precise as we think, and our checkout procedure is a bit complex, so it is a little far away from the application. There have been many methods to discover this disease, such as FISH and blood routine examination, and our approach is much less mature. We found some drawbacks to our investigation and learned a lot from the interview.
Although our method has drawbacks, we compared our approach with a classic method, Flow Cytometry. We found this method much more costly than ours, which means our approach is practical. If the price is low, People can use the plasmid sensor in routine examinations. Therefore, more patients can find out whether they get MDS or not. In addition, we need to make different attempts in clinical application, together with other methods to assist in the diagnosis of MDS, such as bone marrow biopsy, PCR, flow cytometry analysis, etc.. And, it is worth noting that mutations in the SF3B1 gene are also closely related to the prognosis of MDS. Our project will also provide some assessment of the prognosis of MDS patients.
When we came back to the lab, we knew what we could improve and how our project could be helpful in the medical world. Hence, we got a lot from this interview.
3. Interview with Dr. Li
We also did an email interview with Dr. Li, a professor at the University of Chicago. We asked him several questions, and he answered with helpful details. First, we asked about the relationship between splicing abnormalities and disease. According to Dr. Li, MDS is characterized by a high occurrence (> 30% for most; higher for some MDS subtypes) of mutations in SF3B1, which causes specific defects in splicing. More generally, in other cancers/diseases, it's harder to predict which genes are affected and the associated molecular defects. Dr. Li hasn't heard of clinical research about detecting or staging blood disease based on splicing abnormalities, but he thinks it is an attractive study area. The key would be to show that it's easier to detect RNA splicing defects caused by SF3B1 or other recurrently mutated splice factors, like U2AF1 than loss-of-function mutations directly in SF3B1 or U2AF1. The main idea here is that there are more RNA copies per cell than DNA copies and defects in splicing, which may improve detection via RNA. He can see diagnosing disease based on the detection of RNA splicing abnormalities becoming more prevalent in helping diagnose mendelian/rare diseases because currently, the most common genomic assay used is exome sequencing to find nonsense, nonsynonymous, and obvious splice-altering variants. However, it has been shown that many splice-altering variants are outside canonical splice sites and, thus, hard to detect.
Figure 11 Interview with Professor Li via Email
He likes the project overall because it sounds like a lot of fun, and not everything needs to be directly useful to be informative/a good idea. He thinks our approach of taking bone marrow biopsies from the patients and trying to culture the cells and transfect your plasmid sensors into these cells is complicated. He suggests we can try cell free system, which inspires us to perform the experiment in Proof of Concept.
4. Interview with Dr. Zheng
In August, we interviewed Dr. Zheng, an expert in blood system disease and introduced our present project. Firstly, Dr. Zheng complimented our thorough understanding of the background of MDS and told us more about the causes of MDS, the disease discovery rate is getting higher. The specific etiology of MDS hasn't been clear so far in the current research. Even in aspects of its diagnosis and treatment, the treatment is not as thorough as acute leukemia, and we need to exclude other diseases to diagnose MDS. Because the etiology of MDS is unclear, it's hard to prevent. Moreover, since MDS is a clonal disease of hematopoietic stem cells, it must have something to do with genetics. MDS is more of a process of genetic mutation accumulation; it often develops the disease in middle and old age, increasing the incidence in the elderly. We don't know how far mutations have accumulated, so a healthy lifestyle is the best way to avoid MDS. In addition, some external risk factors include longtime exposure to some chemicals, lack of nutrition, and other external stimuli, such as radiation and some chemotherapy drugs in some tumor patients.
Figure 12 Interview with Professor Zheng
Dr. Zheng also answered us about the current testing for MDS. One of the most traditional methods is for doctors to take a patient's bone marrow to smear or slice the patient's tissue and see it under a microscope. Morphology can see a whole cell structure and changes. Also, immunology is generally used to detect the loss of the number of cells. It is an indispensable means in many blood tests. However, in MDS, it is not as helpful because MDS may have many atomic cells, and it is just a pathological hematopoietic. MDS does not have pronounced characteristics, so doctors have no way to provide definite evidence of MDS. The cost of lost cytometry is about 2500 RMB, and chromosome testing is 600. If a further probe for the chromosome is needed, the price is 1,000 RMB. The total is about 5000 RMB. She believes the status of RNA splicing in patients can be used to diagnose MDS. In her lab on MDS, they included second-generation sequencing to detect mutations in these genes related to RNA splicing. Such features are beneficial. They have already been using these abnormal mutations, but the cost is very high for most patients, and she's happy that we are trying to address the cost problem of diagnosing MDS and encourage to do more in the lab.
In terms of our project, Dr. Zheng thinks it does work technically. Nevertheless, she notified us to consider the clinical application. Situations are very different and complicated in clinical cases. So, we need to test the possibility of false positives and negatives. Also, in actual clinical applications, conditions may be deviated from what we think, and we need to consider such derivations and learn from them.