Abstract
Gene editing technology is the behavior of artificially modifying or changing the gene sequence of host cells, and its practical application and development have brought many ethical risks to human society. In order to ensure the healthy and orderly development of gene editing technology, we should take a cautious and responsible attitude towards its practical application and pay attention to its risk prevention. In the aspect of ethical risk management, we should distinguish different types of gene editing behavior and establish a classified management mechanism. Gene therapy should generally be allowed. For gene enhancement, the pursuit of special endowment should be strictly prohibited. The behavior of gene editing in germ line should be resisted in principle and allowed only when exceptions are made.
INTRODUCTION
Life science research has made remarkable progress and development in the 21st century, which has made historic breakthroughs in such varied fields as production, military affairs, environmental protection, and medical care 1 , and will lead the human society from the “information age” to the “biological age”. 2 In the field of gene bioengineering, with the safety of gene editing technology and the increase in its social acceptability, it is possible to apply and popularize gene therapy in clinical settings. Clinicians can use technical means to achieve fixed-point knockout and change of patients’ diseased genes, as well as synthesize gene drugs for the target site of gene mutation, to achieve “precise treatment” of diseases 3 . However, the dual nature of technology is inevitable. While gene editing technology may provide significant benefits for society, its potential for causing or creating problems also exists, which brings many ethical and legal problems to society. 4 At this time, we urgently need to ask where is the ethical boundary of the development of human gene editing technology?
THE BASIC OVERVIEW OF HUMAN GENE EDITING TECHNOLOGY
“Gene editing” means “recombinant” DNA, which is a technology that can accurately modify the genome or transcript and can complete gene site-directed mutation, knockout or knock in of fragments, etc. similar to “cut” and “paste” procedures in computer programming. In 1970, Berg and David Jackson successfully connected a piece of DNA from bacterial virus and three genes from E.coli to the complete SV40 genome, which achieved a breakthrough in the combination of biological genes and laid a solid foundation for the later gene editing project. Gene editing technology was first widely used in the field of animals and plants. For example, the world's first fertile transgenic plant, herbicide-resistant transgenic tobacco, was successfully developed in Belgium in 1983, and then it was widely used in the cultivation and improvement of rice, corn, cotton, soybeans, rapeseed, potatoes, etc. The resulting genetically modified foods such as edible oil and bean products quietly entered people's kitchens and came to our dining tables. The great success of gene editing technology in the fields of microorganisms and plants has made people eager to turn their attention to the field of animals, including human society. The first transgenic animal in the world is to introduce the growth hormone of rats into the fertilized eggs of ordinary mice and cultivate a mouse twice as big as ordinary mice. Then, under the guidance of this technology and method, transgenic rabbits, transgenic pigs, transgenic sheep and transgenic chickens were born one after another.
In the field of clinical practice, human gene editing technology can be divided into gene therapy and gene enhancement according to its purpose of use. Gene therapy is for medical purposes, adjusting human defective genes at the DNA level to achieve the normal gene level needed for life activities, so as to achieve the purpose of treating and preventing diseases. Gene therapy is clinically applied to the early diagnosis and late treatment of genetic diseases, such as cystic fibrosis and hemophilia. 5 Recent years, with the maturity and popularization of the new generation of gene editing technology represented by CRISPR/Cas9, gene therapy has become more simple and easy in clinic. 6 Gene enhancement does not aim at simple treatment. It aims to enhance human appearance and ability by introducing non-therapeutic target genes into human recipient cells and expressing them in specific protein. At the same time, according to the different types of target gene receptor cells, it can be divided into somatic gene enhancement and germ cell gene enhancement. Gene enhancement is based on people's worry or dissatisfaction with their own natural traits, and the natural expression of genes is influenced by gene intervention technology to realize the vision of a better life and a happy life.
A brief classification of human gene editing techniques is shown in Table 1.
Brief Classification of Human Gene Editing Technology
Ethical risk of human gene editing technology
Human gene editing technology is the behavior of artificially modifying or changing the gene sequence of host cells, and there are the following ethical risks in its clinical practice and application.
Technical Security Risk
At present, there are still some defects in human gene editing technology, such as low efficiency, insufficient accuracy and fidelity. 7 It is rashly applied to human experiments or clinics, it may cause serious adverse consequences.
Eugenics Risk
Gene editing technology is generally used in clinic because we found the defective gene components in human body, so we want to knock them out through technical means. It is acceptable to help individuals with genetic diseases to achieve physical health through gene editing technology. However, if the use of gene editing technology goes beyond medical purposes, such as achieving “customized babies” or gaining some genetic advantages, it involves the following questions: Do people have the right to screen genes excessively? How to establish the identification and screening mechanism of good and bad genes? Do the so-called “defective” genes eliminated by technology deprive future generations of the right to choose “bad” genes? Does artificial gene selection block many potential possibilities of human future development? This kind of gene intervention means hides the risk of excluding some “bad genes” and “inferior people” from social life, which will lead to new racial discrimination.
Humanity Remodeling Risk
The object of human gene editing technology is human genes. This practice presents irreversible technical consequences in clinic, and genes are related to human natural external characteristics and genetic laws. If editing is aimed at human germ cells, the consequences of this technology will be embedded in the root node of “sexual reproduction” and will be passed down from generation to generation, which will have an intergenerational impact and eventually disturb the water of the whole “human gene pool". If private individuals are allowed to modify others' “genes” at will, then in the near future, everyone may be at risk of being modified at will by others, which will seriously violate the basic bioethics principles such as autonomy, harmlessness and justice. 8 If an individual can be reduced to the product of others' arbitrary decision and transformation, then his life integrity will also be destroyed, and human subjectivity and autonomy will gradually disappear.
Liability Attribution Risk
The normative logical premise of the law itself is that the actor is a completely independent and autonomous individual in thought and behavior, and he can freely control his words and deeds and bear legal responsibilities related to it. Gene editing technology is aimed at the genes of recipient cells. Will it eventually affect human consciousness? Will it cut off the causal chain of investigating the legal responsibility of the perpetrator? If gene editing has changed the actor's ability to identify, judge and choose his meaning and behavior, will it be biased to “criticize” the actor in law and demand him to make a correct and legal choice in the real situation? In this case, is it justified to investigate the legal responsibility of the perpetrator? This questioning has created problems and risks in the attribution of legal responsibility.
The Ethical Boundary of Human Gene Editing Technology
In recent years, with the continuous upgrading of gene editing technology in clinical practice, especially the maturity and popularization of CRISPR/Cas9 gene editing technology, it has become more and more simple to modify and change the human genome sequence at fixed points, which has achieved good results in the treatment of hereditary diseases such as cystic fibrosis and thalassemia, and the post-genome era of “gene diagnosis” and “gene therapy” has gradually arrived. 9 However, although people have made great achievements in solving the genetic mystery of life, facing the complicated physiological structure of human body and hundreds of millions of colorful cell groups, science has not had time to discover countless “dark matter” hidden in human body and playing an important role in life activities. The exploration and revelation of human life activities and genetic information is only the tip of the iceberg in complex life activities. Therefore, gene editing based on the limited information of human life activities will inevitably bring many potential unknown risks.
As mentioned above, human gene editing technology can be divided into “gene therapy” and “gene enhancement” according to whether it aims at medical treatment or not. “Gene therapy” is aimed at medical treatment, and what it wants to achieve is the early prevention and treatment of some hereditary diseases. Because it is a legitimate interest demand of individuals to maintain their basic interests in life and health, such interests are related to their most basic survival and development interests, and should be respected and protected in the general sense of society and supported in ethical practice. In a narrow sense, “gene enhancement” is not aimed at medical treatment, but to meet the needs of personalized “personal tailor” and realize “perfect” life hope. At present, there are two completely different attitudes about “gene enhancement” in academic circles. A supportive attitude holds that in a liberal society with diverse values, individuals enjoy independent rights, and respecting “gene enhancement” shows respect for independent rights, and “gene enhancement” can transcend human nature and avoid some weaknesses in human nature, which has great social value and should be supported in practice; The other is skeptical or even negative, and its representative figures are Habermas and Francis Fukuyama. For the protection of human nature, they oppose any non-medical gene intervention. They think that “gene enhancement” is not just a respect but a violation of the principle of autonomy and equality claimed by liberalism, and accuse people who support “gene enhancement” of destroying individual autonomy despite the slogan of respecting autonomy in name. Under the technology of “gene enhancement", people's inner essence and meaning of existence are constantly being dispelled by external forces, and their independent life history is constantly being invaded or even rewritten by the outside world, and people may passively become the product of manipulation by others, which runs counter to the content and requirements of autonomy. 10 At present, the legal supervision of human gene editing technology in the world mainly adopts the classified supervision mode, and the law generally allows the behavior of somatic gene editing; As for germ line gene editing technology, there are great legal disputes in various countries, and there are three different modes: permission, prohibition and exception prohibition. The representative legislative example of “allowing” mode is the United States (but only private funds can be used); The representative legislative examples of “prohibition” mode are Germany and France; The representative legislative example of “exceptional prohibition” mode is Britain. 11 Comparing the above different modes of supervision, the author believes that it will be out of date for legal supervision to adopt a completely forbidden mode or a completely free mode at the moment when the new biomedical technology represented by human gene editing technology is developing rapidly. Considering the extensive involvement of human gene editing behavior, which involves conflicts in ethics and moral values of many different stakeholders, and considering that gene editing technology, as a new biotechnology, is not perfect in its own development, it has potential ethical risks in clinical practice. Especially for the gene editing of germ cells and embryos, this technology has irreversible consequences in clinic. The result will not only affect the experimenter personally, but also be passed down from generation to generation through genetic material, affecting the “well-being” of future generations. Therefore, from the perspective of promoting the benign development of human gene editing technology, we should take a cautious and responsible attitude towards its research and application, and pay attention to its risk prevention and control and legal governance. In terms of specific treatment measures, we should strictly distinguish between gene therapy and gene enhancement behavior. Gene therapy should generally be allowed. As for gene enhancement, considering that there are many ethical and legal disputes behind it, it is prudent to ban the behavior of individual gene enhancement that pursues special endowments. In principle, we should resolutely resist the behavior of gene editing in reproductive system. Only when the following necessary conditions are met can they be allowed by legal exceptions:
First, there is an urgent need to prevent cystic fibrosis, thalassemia and other genetic diseases.
Second, there is no other alternative technical operation scheme in clinic.
Third, any use of germ cell gene editing technology must go through technical safety screening. It can only be used on the basis that the upstream basic research, the midstream clinical experiment and the downstream clinical application have all passed the safety inspection.
Fourth, before gene editing of human germ cells, it needs to be examined and approved by the ethics Committee of the unit.
Fifth, after being examined and approved by the unit ethics committee, it needs to be reported to the regulatory authorities for examination and approval. If it is not approved, it may not be implemented.
Sixth, the approved genetic editing behavior of germ line should meet the statutory time limit, and the internationally accepted “14-day rule” can be used as a reference, and the samples or recipients edited by genes should be destroyed within the statutory time limit. 12
CONCLUSION
The research and exploration of molecular biology based on genes has achieved great changes in the field of biology, and its behavior and consequences have penetrated into every aspect of people's daily life, which has had a profound impact on human politics, economy, culture, society and ecology. With the 21st century, gene editing technology has developed rapidly in the field of clinical practice, and a large number of “gene therapy” techniques have flooded into the clinic, which has given birth to new changes in clinical medical care, and the era of “precise therapy” in clinic has gradually arrived. 13 However, the development of technology is always a “double-edged sword". While gene editing technology shows its excellent social quality, its potential of “causing" or “creating" problems is gradually discovered, which brings more ethical and legal problems to society. Facing the progress and challenges of human gene editing technology, we urgently need to let morality and reason participate in it, play and collide with each other, respond to moral conscience in a responsible manner, and then achieve balance in reflection and harmony in human practice.