Ethics Discussion
Synthetic biology, as a newly-presented sub-discipline of life sciences, has appealed to lots of researchers devoting themselves to it. As the world has got insights into the information covered by the genes, they’ve mastered their biological functions. It is just like an engineering job that these biobricks are assembled by synthetic biologists to become a biological device, which can complete novel tasks. From the moment it emerged, it moved towards the public accompanied by many controversial topics. A large portion of people stoutly negates the field with the viewpoint that it is as frightening as ‘human cloning’.
At the present, the basic ideas in synthetic biology include two lines. One is to design and build new biological parts, modules and system. The other is to redesign the natural biological systems. Both ideas are for the benefits of human society. Obviously its task is to standardize the genetic information and manufacture operable standard biological parts. However, it seems on the opposite side with the biodiversity of the nature. How can we resolve this kind of contradiction? And how do our human beings look upon the numerous social problems it causes such as the patents and impartiality?
Figure 1. The genomic map of the Mycoplasma laboratorium, a chemically synthesized bacterium, also called “Synthia”. The creation of Synthia has triggered heated bioethical discussions on synthetic biology.
The ultimate aim of synthetic biology is to synthesize a completely artificial life, which is notwithstanding fascinated to many of us. Nevertheless, it makes the whole society feel terrified to the unknown vita. In that way, whether or not we should advocate this kind of creativity for life? And how can we evaluate the benefits and risks in synthetic biology? Or how can human beings find a balance of the double-edged sword?
To find the answers to all the above questions, we’ve conducted a discussion on the ethical issues in synthetic biology with Doctor Xie Guangkuan of the Institute of Medical Humanities of PKU. At the same time, we estimated our project on ethics according to the Three Principles of Bioethics.
The First Principle: BENEFICENCE
Figure 2. Three of our team members are discussing with Doctor Xie Guangkuan from the Institute of Medical Humanities, Peking University.
Compared with other traditional detection methods, the biggest advantage of the detection of nucleic acid is the great shortened of the time without the decrease of the specificity and sensitivity. And not to mention the influence of time cost on the economy of a gradually developed society, only consider its role in the prevention and cure of tuberculosis is enough to make people wonder. In the diagnosis and treatment of TB, traditional methods, such as bacteriological detection methods, need one to two months to get the result, while in clinical work, no doctors dare to give treatment after such a long time waiting for the result, because the disease may develop rapidly during the waiting time, which may lead to irreversible consequences. Therefore, in the current clinical work in China, treatment would be given first while waiting for the detection result of bacterial culture. This is indeed a way to avoid the development of the disease, but for the misdiagnosis patients, on the one hand, the right treatment has been delayed, on the other hand, the wrong treatment may lead to the resistance to anti-tuberculosis drugs. Nucleic acid detection can effectively avoid these problems, the existing mature detection technology of Mycobacterium tuberculosis usually takes only a few hours to get the result, which can greatly reduce the detection time and is more conducive to the realization of the treatment after diagnosis, which thus can avoid delay treatment and error treatment.
Although nucleic acid detection has much advantage compared to traditional detection method, the detection of nucleic acid is still not able to replace the traditional detection method. The main reason owes to its expensive price. Besides that, the traditional detection method has been developed for many years, and through the traditional detection, the staffs can see mycobacterium tuberculosis directly, which give them more confidence on making a definite diagnosis. Thus as a new method which gives the result through an indirect way, nucleic acid detection method is refused from the idea of part of doctors. And in this paper, we will focus primarily on the former: the advantages and disadvantages of nucleic acid detection in the economic analysis compared with the traditional detection method. Through consulting Beijing research institute for tuberculosis control, we have learned that the current traditional smear technology price is about 15 yuan, and 60 yuan for bacterial culture, that is, the price of traditional detection method is about 100 yuan, and the current method for nucleic acid detection such as Hans needs 525 yuan, X-pert detection technology needs 650 yuan, which means the detection method of nucleic acid is about 5-6 times as much as the price of traditional methods, leading to the conflict psychology for patients to use nucleic acid detection method. In addition, as for the hospital, the cost of traditional detection method is relatively low, while providing nucleic acid detection method, hospitals need to be equipped with more expensive equipment, according to the introduction of the lab director from Beijing Research Institute for Tuberculosis Control, the construction of the current nucleic acid detection platform costs tens of thousands or even hundreds of thousands, although most large hospitals have the ability to afford this instrument. However, for small or medium hospitals, it is still difficult to be equipped with such expensive instruments. And dramatically, the incidence of tuberculosis in China in rural areas is much higher than urban areas, which means most of the tuberculosis patients cannot use nucleic acid detection method. Thus no matter from the view of hospital or patient, the use of nucleic acid testing is out of affording, which leads to the limitation of its application.
And our project which is also based on nucleic acid detection has given a clever solution to the problem. We concentrate the detection process in a handy container. The first to avoid the need for nucleic acid detection laboratory platform, which thus can solve the problem for small hospitals to withstand the high cost of laboratory established. On the other hand, our instrument uses a new principle of work and cost much lower compared with the previous nucleic acid detection method.
And our project which is also based on nucleic acid detection has given a clever solution to the problem. We concentrate the detection process in a handy container. The first to avoid the need for nucleic acid detection laboratory platform, which thus can solve the problem for small hospitals to withstand the high cost of laboratory established. On the other hand, our instrument uses a new principle of work and cost much lower compared with the previous nucleic acid detection method.
The Second Principle: EQUITY
Figure 3. Doctor XIE Guangkuang led us to think in the way of “Three Principles of Bioethics” during the discussion.
Whether in China or in the world, the gap between the rich and the poor, the inequality of regional resources is a problem that we cannot ignore. When the unequal distribution of resources comes to the diagnosis of Mycobacterium tuberculosis, the incidence of tuberculosis is getting worse caused by the delayed diagnosis of tuberculosis in relatively backward regions. We take Beijing Research Institute for Tuberculosis Control and the Center for Disease Control of ZhengHe in Fujian Province as the representative of the developed cities and remote mountainous areas, and detailed consultations with the two agencies have been made. As expected, Beijing Research Institute for Tuberculosis Control has a variety of innovative nucleic acid testing equipment, although they said these devices are indeed expensive, not often used in clinical, but they have these conditions. And for Center for Disease Control of ZhengHe in Fujian province, it has only the traditional detection facilities, no conditions to build a nucleic acid detection platform. What’s worse, for the region's people, the majority have no economic ability to bear the cost of nucleic acid detection. This has led to the unfairness in the detection of Mycobacterium tuberculosis, and the economic level is the detection means of the watershed.
As stated above, our project is trying to put a set of nucleic acid detection in a small container, in line with the concept of Point-Of-Care, making a detection which is cheap, convenient and simple. Such a set of equipment will be able to minimize the embarrassment brought by the differences in the region. And the relatively backward areas can have the opportunity to use the new methods to reduce the time of the detection of tuberculosis, and improve the detection specificity and sensitivity, even in the absence of qualified laboratory conditions.
The Third Principle: RESPECT
As a country whose incidence of tuberculosis is ranked second in the world, there are lots of TB patients in China. And according to the relevant laws and regulations in China, the TB patients are limited in certain industries such as teachers. In catering and other industries, people are required to have the certificate issued by the hospital to prove they are not the TB patients. If TB detection becomes easier, it is expected that this part of unit can be equipped with such a testing tool for practitioners to verify, and even other industries will hope that their employees are not TB patients, thus they may be equipped with the appropriate testing tools as well. Although doing so is beneficial to the control of tuberculosis, it can also make the patients feel that their privacy is not protected, and they may feel social discrimination and disrespect. For this case, we do not think that it can be the reason for the detection of nucleic acids should be fixed. The state should take other measures, such as the restriction of enterprise or institution to buy such disease detection tools, etc.
CONCLUSION
To sum up, we believe that the project we are working on is in line with the principles of ethics, which will help to promote human health, and to some extent improve the imbalance of social medical resources.
Economics
Introduction
The overall goal for control of Tuberculosis (TB) is to ensure prompt identification and treatment of infectious patients, and to eliminate TB ultimately. Global progress was seen in last two decades, but not enough to reach the aim of TB control, where detection method is the major limitation
There are various detection methods. Sputum smear microscopy remains the mainstay of TB diagnosis in China and other resource-constrained countries, which is inexpensive but not sensitive particularly in people with HIV and in children, while culture serves as the current reference standard but takes weeks and requires laboratory capacity. Rapid molecular tests to diagnose TB and drug-resistant TB such as Xpert requires expensive equipment and trained laboratory staffs, making it not widely adopted in China. With the low percentage (37%) of new pulmonary cases that were bacteriologically confirmed, China accounted for 11% of the 5.7 million new and relapse cases of TB that were notified in 2013 [1]， which has an urgent need for accurate and rapid detection methods.
Peking iGEM 2015 develops a detection device using the CRISPR/Cas9 system. We have shown that CRISPR/Cas9 systems can be engineered to target specific DNA sequence of Mycobacteria tuberculosis by using a mutant of Cas9 nuclease without double-stranded endonuclease activity (dCas9) and two “guide RNA” with complementarity to specific DNA target site screened by bioinformatics. Fusing dCas9 with split reporter proteins, the signal can be easily read out.
What is the supply and demand in TB testing market? Can our device really be applied to TB diagnosis in China? Is there any possibility that advanced molecular tests will replace traditional methods? Are there other features should our device have? To find the answers to these questions, we’ve conducted a discussion on the economic issues with Mr. Ding Beichuan, Director of Center Lab of Beijing Research Institute for Tuberculosis Control.