At present, there is no special legislation on gene editing in China, and the relevant provisions and rules are scattered; the specific concept is not clear. As the prevention principle will affect the risk and benefit of human reproductive interventions, it is necessary to pay attention to the risk of gene editing on the health of offspring in practice. It is suggested that new biotechnology regulatory programs should be introduced in China and international supervision and cooperation should be strengthened. The focus should be on the process of using gene editing technology to create products rather than the products themselves. In order to maximize the contribution of gene technology to human beings, it should carry out human embryo research under ethical norms.
In March 2020, a major breakthrough was made in Oregon Health and Science University in Portland to address a blindness-causing gene mutation. The procedure marks the first time Clustered Regularly Interspaced Short Palindromic Repeats (hereinafter referred to as CRISPR) has been used to edit human genes within the body, which is also called in vivo gene editing. Previous gene editing methods have involved editing genetic material after it was removed from the body. The trial’s gene editing approach is designed to be permanent, but not passed onto the offspring of those who receive it.
CRISPR is a family of DNA sequences found within the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments from viruses that have previously infected the prokaryote and are used to detect and destroy DNA from similar viruses during subsequent infections. The CRISPR-Cas9 gene editing technology is another major breakthrough after the Transcription Activator-Like Effector Nuclease gene editing technology. The CRISPR-Cas9 system has higher gene editing efficiency, while the Cas9 system is more convenient to construct and use, and has been applied to various species. This technique allows specific DNA editing of targeted genes by RNA-directed Cas9 nucleases. It is a widely used gene editing technology.
Globally, cell and gene therapy has not only changed the way humans treat genetic diseases and intractable diseases, but also is disrupting the entire pharmaceutical ecosystem. By the end of 2019, more than 27 cell and gene therapy products have been launched globally, and about 990 companies are engaged in the development and commercialization of next-generation therapies. The global cell and gene therapy market is expected to exceed 11.96 billion USD by 2025.
With policy support, China has become a fertile ground for global cell and gene therapy development. From 2017 to 2019, more than 1,000 clinical trials have been carried out or are in progress. On November 6, 2019, the National Development and Reform Commission of the People’s Republic of China officially released the Industrial Structure Adjustment Guidance Catalog (2019 Edition), which was implemented from January 1, 2020. Children’s drugs, shortage drugs, gene therapy drugs, cell therapy drugs, etc. were added to the encouraged category for the first time in Chinese Mainland. The Adjustments of Industrial Structure Adjustment Guidance have always been regarded as the ‘weathervane’ of industry development in Chinese Mainland, from which the overall can see the Chinese government’s current support direction for industrial development. Chinese government has granted thousands of related patents, and is ranked second in the world. 45 local companies and 4 joint venture companies have led the booming development of China’s cell and gene therapy biotechnology industry, and have approved cell and gene therapy new drug clinical trial applications.
However, law has had a permanent and troubled relationship with science, and the key factors that promote the prosperity and development of China’s cell and gene therapy industry include clearer regulations and industry quality standards. The misuse of science within the legal realm, as well as human societies failed attempts to make law more scientific, is well documented. The cause of these problems is less clear. It is tricky that the more human beings touch gene editing, the more questions there are.
On December 30, 2019, according to the National News Agency, Xinhuanet, the First Gene-edited Baby case was publicly pronounced. Judges of the People’s Court of Nanshan District of Shenzhen found that the three defendants, He Jiankui, Zhang Renli and Qin Jinzhou jointly illegally implemented human gene editing and reproductive medical treatment for reproduction, and the court determined these activities constituted the crime of illegal medical practice. The former Associate Professor He Jiankui was sentenced to three years in prison with a fine of 3 million yuan. Zhang Renli, a member of the medical institution in Guangdong Province, was sentenced to two years in prison with a fine of 1 million yuan. Qin Jinzhou, another member of the medical institution, was sentenced to two years’ probation under a suspended sentence of one year and six months’ imprisonment with a fine of half a million yuan.
On November 26, 2018, a scientist in China claimed to have created the world’s first gene-edited babies, in a potentially ground-breaking and controversial medical first. The babies’ names are Lulu and Nana, he said in one video. If true, it would be a profound leap of science and ethics. This kind of gene editing is banned in most countries as the technology is still experimental and DNA changes can pass to future generations, potentially with unforeseen side-effects.
Chinese researcher He Jiankui made the claim in interviews with the Associated Press. In an earlier telephone interview and emails with Reuters, He Jiankui said he was aiming to bestow on the gene-edited babies ‘lifetime protection’ against HIV that causes AIDS. He also spoke about his research with organizers of an international conference on gene editing in Hong Kong. At the meeting, He Jiankui revealed that one of the genetically modified twins would be immune to HIV because both of her CCR5 gene copies have been deleted. Another baby may still be susceptible to infection because a complete copy of CCR5 was inadvertently left in the gene editing process. He said he began his work in the second half of 2017 and enrolled eight couples, all of whom were composed of HIV-positive fathers and HIV-negative mothers. Finally, one couple withdrew. He said in five videos posted on November 26, 2018 that he used a gene editing technology known as CRISPR-Cas9 to edit the genes of twin girls. He said in one YouTube video that the editing process, which he called gene surgery, ‘worked safely as intended’ and that the resulting twins were ‘as healthy as any other babies.’ It was impossible to verify the claim as he did not provide any written documentation of his research.
Many scientists working in genetics say they believe such experimentation is dangerous. And He Jiankui’s claim was immediately condemned by more than 100 Chinese and other scientists as unsafe and unethical. The National Health Commission of the People’s Republic of China said it was ‘highly concerned’ and had ordered provincial health officials to ‘immediately investigate and clarify the matter’. The Shenzhen Medical Ethics Expert Committee said it was investigating the case. The Health Commission of Guangdong Province was also looking into it. China’s Southern University of Science and Technology where the scientist, He Jiankui, holds an associate professorship, said it had been unaware of the research project and that he had been on leave without pay since February 2018.
The details of First Gene-edited Baby case were made public on January 21, 2019: He Jiankui has privately organized a project team that includes foreign personnel since June 2016, deliberately evaded supervision, and used technologies with inaccurate safety and effectiveness. They implemented the gene editing activities of human embryos for the purpose of reproduction, which is banned by the Chinese government. From March 2017 to November 2018, He Jiankui recruited 8 couples of volunteers (male and female negative for HIV antibody) through forged ethical review documents. In order to circumvent the relevant regulations that HIV carriers are not allowed to implement assisted reproduction, they planned to replace volunteers with blood tests, and instructed individual practitioners to perform gene editing on human embryos and implant them into mothers in violation of regulations. In the end, 2 volunteers became pregnant. One of them has given birth to twin girls ‘Lulu’ and ‘Nana’, and the other is pregnant. One of the remaining six pairs of volunteers withdrew from the experiment, and the other five pairs of volunteers were not pregnant.
He Jiankui’s gene-edited baby experiment has sparked extensive discussions on bioethics. Although he said that the gene-edited twins Lulu and Nana were born healthy, there is no report to prove that, and no one has seen the twins. He Jiankui’s experiments received help from American universities and laboratories and even the National Academy of Sciences in US stated in a report in 2017 on human gene editing that it strongly recommends suspending clinical trials of human gene editing unless the trial has a sound and effective regulatory framework. But He Jiankui’s experiments obviously lacks a safe and effective regulatory framework, and even this article suspects that the content of the experimental consent form is misleading.
This article intends to take He Jiankui’s experiments as the starting point for legal review, to comprehensively examine the current legal liability mechanism for the clinical application of human gene editing in Chinese Mainland, and to systematically analyze the legal liability of experimenters from the perspective of interpretation. From the perspective of legislative theory, suggestions for the improvement of the future legal liability mechanism are put forward.
Wei Zexi, a 21-year-old college student from Shaanxi, China, suffered from a rare tumor. He died in April 2016 after receiving several rounds of immunotherapy without regulatory approval in a hospital.
This incident triggered public condemnation, prompting the government to suddenly implement a 19-month ban on cell and gene therapy research and clinical applications. From 2018 to 2019, the Chinese government, led by the National Health Commission and National Medical Products Administration, issued a series of policies to gradually strengthen the supervision of the cell and gene therapy industry. These policies further clarify the corresponding responsibility of different institutions.
Before 2020, the norms and standards of gene therapy in Chinese Mainland were imperfect, and no laws from the National People’s Congress directly regulating gene therapy and gene editing had been formulated. Even the Basic Health Care and Health Promotion Act of the People’s Republic of China which came into force on June 1, 2020, which is applicable to medical and health care, health promotion and supervision and management activities and says nothing on gene editing. Only the Civil Code of the People’s Republic of China from the National People’s Congress sets up several clauses for gene editing and it will take effect on January 1, 2021. There are still some deficiencies in the liability mechanism in the current legal framework in Chinese Mainland.
Before the Civil Code of the People’s Republic of China, the legal sources of human gene editing technology in China are mainly administrative regulations and ethical guidelines, and all these regulations are from departments of the State Council, whose legal effect is lower than laws from the National People’s Congress. The regulations on basic research and clinical research of human gene editing include the Management Measures for Human Assisted Reproductive Technology, the Ethical Guiding Principles for Human Embryonic Stem Cell Research, the Interim Measures for the Management of Human Genetic Resources, the Management Measures on Genetic Engineering and the Administrative Measures for Clinical Application of Medical Technology. The regulations for clinical research and application include the Procedures for Ethical Review of Biomedical Research in Humans, Quality Control Points for Human Somatic Cell Therapy and Gene Therapy, Guidelines for Human Gene Therapy Research and Preparation Quality Control Technology. Among them, Quality Control Points for Human Somatic Cell Therapy and Gene Therapy, Guidelines for Human Gene Therapy Research and Preparation Quality Control Techniques only cover human somatic gene editing, and it is not clear what types of cells can be used for genes. Only the Management Measures for Human Assisted Reproductive Technology directly relates to human germ cells and embryos, which explicitly prohibits buying or selling gametes, zygotes, and embryos in any form, and does not specify whether studies on human embryos and germ cells are allowed. When it comes to human gene editing for non-reproductive purposes, no Chinese rules or regulations could answer the question. The lack of legislation is not conducive to preventing and controlling the abuse of sophisticated technology such as gene therapy, and once someone is injured as a result, they will not be able to provide appropriate protection.
Besides, the current regulatory norms are mainly technical management methods or ethical guidelines, and there are omissions in administrative regulatory measures (no effective coordination between competent authorities in the cross-field supervision of gene editing, human trials, assisted reproduction, etc.). The administrative punishment measures are mild, mainly administrative punishments such as warnings and fines. Because of the omission of the regulatory measures and legal responsibilities directly on the human gene editing test of the reproductive system, in the view of the existing norms, the behavior that should really be punished, such as the clinical application of human gene editing of the reproductive system, instead the general violations behavior.
The Civil Code of the People’s Republic of China clearly stipulates the donation of remains and human organs, human tissues, and human cells. Article 1006 of the Civil Code of the People’s Republic of China stipulates: ‘Persons with full civil capacity have the right to donate their human cells, tissues, organs, and remains free of charge in accordance with the law. Organizations or individuals shall not force, deceive, or induce their donations. If a person with full civil capacity agrees to donate in accordance with the provisions of the preceding paragraph, it shall be in written form, or a will may be made. If the natural person has not expressed his disapproval to donate before his life, after the natural person dies, the spouse, adult children, and parents may jointly decide to donate, and the decision to donate should be in writing.’ Article 1007 of the Civil Code of the People’s Republic of China also stipulates: ‘It is prohibited to buy or sell human cells, human tissues, human organs, and remains in any form. Sales in violation of the preceding paragraphs are invalid’. Article 1009 of the Civil Code of the People’s Republic of China expressly stipulates in the form of a special article: Those engaged in medical and scientific research activities related to human genes, human embryos, etc., shall abide by laws, administrative regulations and procedures, shall not endanger human health, shall not violate ethics, and shall not harm the public interest.
In a word, only two legal requirements are necessary for gene editing in Chinese Mainland now. One is the approval of registration from the government, and the other is the will of both husband and wife.
Including gene editing, medical institutions carry out Human Assisted Reproductive Technology without approval, in violation of the provisions of article 12 of the Management Measures for Human Assisted Reproductive Technology passed by the National Health Commission of the People’s Republic of China (implemented on August 1, 2001), which can be in accordance with penalties imposed in the provisions of articles 44 and 47 of the Regulations on Administration of Medical Institutions passed by the State Council of the People’s Republic of China (amended and implemented on February 6, 2016).
Article 44 of the Regulations on the Administration of Medical Institutions is that any team in a medical institution without practice license in Chinese Mainland and authorization, the health administrative department of local government at or above the county level shall order it to stop activities, confiscate illegal income, drugs and equipment, and may impose a fine of not more than 10,000 yuan according to the circumstances. While article 47 of the Regulations on the Administration of Medical Institutions is that any activity beyond the scope of registration, the health administrative department of local government at or above the county level shall warn them and order them to make corrections, and may impose a fine of 3,000 yuan or less according to the circumstances; if the circumstances are serious, their practice license of medical institution in Chinese Mainland shall be revoked.
When it comes to the will of both husband and wife in the action of gene editing, under article 32 of the Basic Health Care and Health Promotion Act of the People’s Republic of China, citizens receiving medical and health services shall have the right to informed consent in accordance with the law regarding medical conditions, diagnosis and treatment plans, medical risks, and medical expenses. If operations, special examinations, and special treatments are required, the medical and health personnel should promptly explain to the patient the medical risks, alternative medical plans, etc., and obtain their consent; if it is impossible or inappropriate to explain to the patient, it should explain to the patient’s close relatives, and obtain their consent. If the law provides otherwise, the provisions shall be followed. Carrying out clinical trials of drugs and medical devices and other medical research should abide by medical ethics, pass ethical review in accordance with law, and obtain informed consent.
No matter before or after the Civil Code of the People’s Republic of China emerges, under the explanation from the Supreme People’s Court and related cases, the true meaning of the two parties is that husband and wife voluntarily choose to gene editing during the marital relationship, and there is no party that infringes the other party’s reproductive rights. The effective proof is the husband and wife voluntarily agree and sign a written informed consent form, while the children should be informed of the informed consent of the children and sign a written informed consent form.
If the parents of the baby born by gene editing and the medical institution where He Jiankui did form a medical contract relationship, the parents of the baby have the right of informed consent. Before the Basic Health Care and Health Promotion Act of the People’s Republic of China and the Civil Code of the People’s Republic of China, according to the Procedures for Ethical Review of Biomedical Research in Humans issued by the National Health Commission of the People’s Republic of China in 2016: Project researchers should obtain informed consent signed voluntarily by subjects; if subjects cannot express written consent, project researchers should obtain their verbal informed consent and submit process records and supporting materials. Informed consent should contain necessary and complete information and be expressed in words and phrases that the subject can understand. In the process of obtaining informed consent, the project investigator should explain to the subjects item by item in accordance with the contents of the informed consent, including: the purpose, significance and expected effect of the research project in which the subjects participated, possible risks and discomforts encountered, and the possible benefits or effects; whether there are other measures or treatment programs that are beneficial to the subject; confidentiality scope and measures; compensation, and compensation for damages and free treatment; the right to participate voluntarily and can withdraw at any time, and the contact person and contact information when the problem occurs. The project investigator should give the subject sufficient time to understand the content of the informed consent form, and the subject should make a decision whether to agree to participate in the study and sign the informed consent form.
If a medical institution or its staff fails to provide truthful and comprehensive notification of the risks of off-target and mosaic in the process of gene editing in accordance with the above requirements, it may constitute a medical fault or breach of contract and bear corresponding civil liability. Among them, the most likely risk is that the medical institution or its staff over-exaggerates the possible benefits of gene editing, conceals and underestimates the possible discomfort and risks of this operation. According to He Jiankui, he had explained the purpose of the experiment to the subjects, and told them that they have never had human embryo gene editing experiments before, and also informed the subjects of the risks of the experiments. However, as far as the public information, there is a consensus in the medical community at that time; there were many medical methods to avoid infants being infected with AIDS. Existing treatment methods can completely achieve mother-to-child blockage of AIDS, and there is no need to edit the babies’ genes.
Under normal legal circumstances, the right to dispose of embryos belongs to both husband and wife, and cannot be donated, bought, or inherited. The treatment of embryos should be informed by the husband and wife otherwise no treatment should be carried out. Without the informed consent of one of the parties and the signing of the informed consent form, the other party initiates the frozen embryo and performs the embryo transfer operation, which violates the will of the uninformed party, and the uninformed party is a simple sperm (oval) donor. So, uninformed parties and future generations do not constitute legal parent-child relationships and do not assume any responsibility in Chinese Mainland.
According to article 16 of the General Rules of the Civil Law of the People’s Republic of China, which is valid for He Jiankui in 2018, except for cases involving protection of fetal right and interests such as to inheritance or acceptance of gifts, the fetus shall be viewed as possessing capacity for civil rights. However, where the fetus has died at birth, its capacity for civil right is viewed as never having existed in Chinese Mainland, which is called ‘starting from birth, finally dying’. Article 16 of the Civil Code of the People’s Republic of China uses the same sentence of article 16 of the General Rules of the Civil Law of the People’s Republic of China.
In the process of undergoing gene editing technology to transform and form embryos, He Jiankui and his team staff edited the genes that have not yet formed a fetus. When damage is caused to the baby after birth, it will eventually be due to aggression (gene editing behavior). The baby was not born at the time of the incident, and the baby is not the subject of the corresponding rights, therefore does not constitute an infringement of the rights of the baby, the team so as to defend and refuse to bear the responsibility.
In other words, regardless of any future health problems related to the children whose genes have been edited, in the existing legal system in Chinese Mainland, children do not have the status of civil litigation, and their parents can only rely on the medical contract or medical damage liability (infringement of the patient’s right to informed consent) and the prosecution of medical institutions, the scope of compensation available will also be very limited.
In addition, gene editing might bring in criminal law risk. First of all, based on the above-mentioned principle of ‘starting from birth, finally dying’, the individuals who perform gene editing operations will not constitute intentional homicide or intentional injury crimes, because they are faced with human ‘gene fragments’, and it is not a ‘person’ composed of genes in Chinese Mainland. Secondly, the scientific cognition and reasonable definition of ‘medical behavior’ may have a greater impact on the qualitative editing behavior of the gene.
The definition of medical behavior in the traditional doctrine and practice circles is based on the purpose of ‘diagnosis and treatment’. For example, the ‘medical behaviors’ in the Implementing Regulations on the Administration of Medical Institutions (implemented on April 1, 2017) include: (1) Diagnosis and treatment activities, which refer to the use of drugs through various examinations, equipment and surgery, etc., to judge the disease and eliminate disease, relieve the disease, relieve pain, improve function, prolong life, help patients recover health activities. (2) Medical beauty, which refers to the use of drugs and surgery, physical and other damage or invasive means of beauty. However, with the advancement of the times, the development of science and technology, the improvement of medical standards, the gradual promotion of social welfare, and the changes in people’s values, the fields in which physicians and other medical practitioners provide services for people have expanded, and medical services have served humanity. The scope includes not only therapeutic behaviors, but also other non-treatment diseases or medical treatments for disease prevention.
Under clause 2 of article 26 of the Practicing Physicians Law of the People’s Republic of China (implemented on August 27, 2009) stipulates that: physicians conducting experimental clinical medical treatment shall be approved by the hospital and obtain the consent of the patient or his family. And non-therapeutic medical behavior is divided into ‘experimental medical behavior’ and ‘other medical practices for the purpose of treating or preventing disease’. ‘Experimental medical behavior’ is further divided into ‘therapeutic experimental medical behavior’ and ‘research experimental medical behavior’: the former is an experimental behavior with the main purpose of clinical treatment of patients, and the latter is accepted whose experiments based on pure scientific research purposes by experimenters (mostly healthy volunteers).
For other medical treatments that are not for the purpose of disease treatment, and for the purpose of prevention, such as non-therapeutic abortion surgery, male and female ligation surgery and artificial reproductive technology, the egg-taking behavior of healthy donors belong to the above range. Therefore, the traditional view of medical behavior has been unable to adapt to the new medical development.
Because medical behavior itself is potentially dangerous, and each human being’s physiological structure has its own uniqueness, medical behavior seems to be inevitable for those who receive medical services, such as: in the face of undiagnosed in the case of trial, drug administration and treatment are not uncommon, but it is difficult to say whether this behavior is medical or experimental.
According to media reports, it is still not known whether He Jiankui and his team, especially the staff who specifically perform the gene editing, have the qualification of practicing doctors. This article believes that the judges of the People’s Court of Nanshan District of Shenzhen hold the broad concept of medical behavior, that is, any behavior that judges and treats human physiology or psychology, belongs to medical treatment behavior. And the judges applied article 336 of the Criminal Law of the People’s Republic of China (implemented on December 4, 2017) for the First Gene-edited Baby case (illegal medical practice).
In He Jiankui’s experiments, the institution he worked for was questioned. Under the current legal framework, the administrative responsibilities directly involved in the illegal human experimentation of ‘gene-edited babies’ are mainly administrative penalties or administrative sanctions such as fines, order for rectification within a time limit, notification of criticism, and warnings. In view of the fact that the human trial of ‘gene-edited babies’ also involves the application of assisted reproductive technology, in fact, it has clearly exposed the problem of ineffective supervision of assisted reproductive technology in Chinese Mainland. However, there are only two liability clauses in articles 21 and 22 in the Management Measures for Human Assisted Reproductive Technology that might apply. Article 21 of the Management Measures for Human Assisted Reproductive Technology is a referral norm, and the behavior of ‘non-medical institutions that carry out human assisted reproductive technology without approval’ shall be governed by article 44 of the Regulations on Administration of Medical Institutions concerning ‘practicing without a medical institution practicing license’. Its administrative responsibilities include ordering the suspension of practice activities, confiscation of illegal gains and drugs, equipment, and fines, while the behavior of ‘medical institutions that carry out human assisted reproductive technology without approval’ shall be governed by article 47 of the Regulations on Administration of Medical Institutions and article 80 of the Implementation Rules of Regulations on Administration of Medical Institutions regarding the administrative responsibilities of ‘diagnosis and treatment activities beyond the scope of registration’, which includes warnings, ordering corrections, fines, revoking medical institutions’ practice licenses, etc.
Article 22 of the Regulations on Administration of Medical Institutions stipulates that seven situations of ‘medical institutions that carry out human assisted reproductive technology’ should be subject to administrative penalties, such as warnings, fines, and administrative sanctions to the responsible persons. The human test of ‘gene-edited babies’ at least meets ‘use sperm provided by institutions that do not have Human Sperm Bank Approval Certificate’. According to article 13 of the Management Measures for Human Assisted Reproductive Technology, the implementation of human assisted reproductive technology must comply with the provisions of the Management Measures for Human Assisted Reproductive Technology, and the Management Measures for Human Assisted Reproductive Technology prohibits the genetic manipulation of human gametes, zygotes and embryos for the purpose of reproduction, and the editing of human embryo genes and their use in reproductive clinics do belong to ‘other violations of the provisions of this approach’ in article 22 of the Management Measures for Human Assisted Reproductive Technology.
The Procedures for Ethical Review of Biomedical Research in Humans also stipulates corresponding administrative responsibilities, including ordering rectification within a time limit, notification of comments, warnings, and sanctions. Article 45 of the Procedures for Ethical Review of Biomedical Research in Humans relates to the administrative responsibility of medical and health institutions and responsible personnel for ‘failure to establish an ethics committee in accordance with regulations to carry out biomedical research in humans’. Article 46 of the Procedures for Ethical Review of Biomedical Research in Humans relates to administrative responsibilities of medical and health institutions and their ethics committees for ‘failure to conduct reviews in accordance with the principles of ethical review and relevant rules and regulations’, ‘failure to file in accordance with regulations’, etc. Article 47 of the Procedures for Ethical Review of Biomedical Research in Humans relates to administrative responsibility of the project investigator for ‘carrying out project research without the review and approval of the ethics committee’, ‘carrying out project research in violation of the relevant provisions of the informed consent’, etc. The project investigator is ordered to rectify within a time limit, and can be notified and criticized or warned according to the seriousness of the circumstances, while the main responsible personnel and other responsible personnel shall be punished according to laws. Article 47 of the Procedures for Ethical Review of Biomedical Research in Humans is more targeted in the investigation of the legal responsibilities of the main experimenters in He Jiankui’s experiments, but the responsibilities are lighter.
Since gene-edited human trials may involve the treatment and prevention of diseases, article 48 of the Procedures for Ethical Review of Biomedical Research in Humans also points to both the Practicing Physicians Law of the People’s Republic of China and the Administrative Measures for Clinical Application of Medical Technology for the possible legal responsibilities of medical and health institutions and project researchers in this situation.
The key words ‘prohibited technologies’ stipulated in article 9 of the Administrative Measures for Clinical Application of Medical Technology include three situations, namely, the safety and effectiveness of clinical application are not accurate; involving major ethical issues; and new medical technologies that have not been demonstrated by clinical research. At present, the human embryo gene editing technology fully meets these three descriptions, and therefore belongs to ‘prohibited technologies’ and cannot be used in clinical applications.
Articles 43 and 45 of the Administrative Measures for Clinical Application of Medical Technology respectively stipulate the administrative responsibilities of medical institutions and medical personnel for ‘carrying out the clinical application of prohibited technologies’. The former refers to article 47 of the Regulations on Administration of Medical Institutions and supplements to serious circumstances, while the latter refers to the relevant provisions of laws and regulations such as the Practicing Physicians Law of the People’s Republic of China.
The implementation of the above-mentioned liability methods faces an embarrassing situation, which is mainly reflected in the lack of pertinence (as mentioned above), insufficient punishment and poor legal effects.
Take He Jiankui incident as an example, in general, human gene editing legislation has certain shortcomings and problems that need to be solved urgently in Chinese Mainland. First, there is no special human gene editing legislation, legislation is scattered, and relevant rules are scattered among various regulations. Second, there is no clear legislative purpose and principle, and there is no unified core legislative concept guidance. Third, the legislative level is low, mostly are from the State Council or its departments, and it has not risen to the legal level for a long time. Fourth, there is no regulation, and there is no special agency responsible for approving and licensing human embryo genetic editing. Fifth, there are a lot of blanks, and the related concepts are not clear. For example, whether the embryos after genetic editing belong to the human body, whether the parthenogenetic embryos belong to human embryos, whether the induced pluripotent stem cells belong to embryonic stem cells, and what types of cells can be used for gene editing research and clinical applications, etc.
In Chinese Mainland, the gene-edited infant technology is currently mainly used in the following fields: the first is gene screening for medical purposes. Gene screening for medical purposes refers to the pre-implantation gene screening for eugenics, so that parents with genetic diseases can have healthy children. This is the most important purpose of pre-implantation genetic diagnosis technology implementation, and it is also the basis and reason why the technology has been widely used and socially recognized. The second is life-saving baby designed for organization matching. The third is gene enhancement for non-medical purposes. Gene enhancement for non-medical purposes mainly includes enhancement of human cognitive ability, enhancement of physical ability and enhancement of emotional ability.
Among the three types of gene-edited infant technology applications, embryo screening and ‘life-saving babies’ are both gene editing for medical purposes. The ethical controversy caused by the application of technology is relatively small. In the process of technology development, attention should be paid to strict and clear technical specifications. And control the indications of different technologies, comply with relevant ethical codes and guidelines, and do not arbitrarily conduct human gene editing under the guise of preventing and curing diseases. Gene enhancement for non-medical purposes is the most ethical controversy, and strict risk assessment is required before the technology is implemented.
Genetic modification (especially CRISPR) is a new technology to change the rules of the world, which will have a positive impact on society and also bring potential threats. Therefore, it is time to establish an ethical and regulatory framework to ensure the development of this technology.
The occurrence of the First Gene-edited Baby case has made the ethical, social, and legal issues of human reproductive system gene editing experiments a hot topic in both public opinion and academic discussions. Before the birth of the CRISPR-Cas9 gene editing technology, complex gene editing was usually performed on mice. However, the emergence of the new tool enabled researchers to achieve precise change in almost any species. Gene editing technologies are more efficient, more precise and less expensive than older methods of genetic modification. It seems that gene editing technology is not yet mature and still too unsafe for human trials, but He Jiankui’s experiments indicate that gene editing has been used for human reproduction. Thus, consideration should be given to the question of whether ethical interventions are permissible.
It is known that gene editing has three potential benefits for reproduction. Firstly, gene editing may allow couples to have a genetically related child without passing on genetic disease. Secondly, relative to genetic selection, gene editing could improve the health of future generations by reducing the frequency of recessive genetic mutations. Gene editing could be used to remove all disease-causing genes from the embryo, or genes associated with elevated risk, reducing the incidence of such diseases in the next and future generations. Thirdly, genetic variants used to decrease risk for some diseases may inadvertently increase risks for others, potentially rendering the recipients of these changes (and their descendants) vulnerable to future health threats.
Gene editing also has three safety risks. Firstly, off-target mutations may cause unintended changes in the reproductive system. Secondly, lack of knowledge of human genetics, current gene editing may cause unintended harm. Thirdly, gene editing may inadvertently increase the risk of other diseases.
There are two options for the Chinese government for gene editing. One option is a total ban on human embryo research. Proponents argue that human embryo research is not necessary for medical purposes because genetically defective embryos can be screened; and research is morally unacceptable and can harm potential life. Opponents believe that gene editing can eradicate genetic defects, and the 14-day rule guarantees that ‘future people’ are not harmed. The other option is setting up comprehensive and systematic special legislation, such as the Gene Medical Technology Law and Human Genetic Resources Management Law should be carried out to form the basic principles of technical regulation. This article considers what role, if any, the precautionary principle should play in our ethical evaluation of gene editing for good supervision in future.
The precautionary principle as a rule of choice has different kinds. The negative precautionary principle means that the activity is not determined to be harmful, and it is not allowed to give up preventive measures. The positive precautionary principle means taking preventive measures when activities may be harmful. The positive precautionary principle can be of various strengths. There are two types of extremes: the strong positive precautionary principle refers to extensive preventive measures against any potential threat to human well-being. The weak positive precautionary principle refers to taking the least precautionary measures based on the threat level to human well-being. The former is too strong and the latter is too weak.
There are also some forms of precautionary principles that explicitly refer to the burden of proof, which requires the event advocate to prove that the activity is sufficiently secure. This article does not specifically address burden of proof requirements. On one view, which this article finds convincing, burden of proof requirements are merely an instrumental means of achieving the precautionary principle’s underlying normative goals. For example, to place greater weight on avoiding some kinds of outcomes than on others.
As mentioned earlier, the negative precautionary principle opposes some arguments for refusing to take precautionary measures, one of which is that no precautions should be taken unless the existence of a particular threat is proven (i.e. sufficient scientific certainty). In this regard, the fifteenth principle of the Rio Declaration on Environment and Development 1992 provides a classic example of the threat of environmental degradation. Although the Rio Declaration on Environment and Development 1992 is widely criticized, it is reasonable. Complete scientific certainty should not be a necessary condition for taking preventive measures, as it has almost never been achieved. Article 15 of the Rio Declaration on Environment and Development 1992: ‘Lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation.’
The negative precautionary principle is considered philosophically meaningless, but historically the regulation of threats such as tobacco and greenhouse gases has shown that it has certain practicability in policy formulation. However, for the gene editing theme, the negative precautionary principle does not give a specific method of weighing the risks and benefits of gene editing, but merely points out that legislation should not scientifically determine its threat to future generations before allowing gene editing.
Unlike negative precautionary principles, positive precautionary principles prescribe a specific approach to decision-making when human society faces threats to human health or the environment. The standard cost-benefit analysis recommends the action plan with the highest expected utility, while the different forms of the positive precautionary principle recommend replacing the standard cost-benefit analysis with more explicit risk management precautions. There are two grounds for the objection to the positive precautionary principle, which are conservativism objection and incoherence and superfluity objections.
Conservativism objection holds that positive precautionary principle has set the threshold for technological progress too high and too conservative. One version of this objection believes that existing cost benefit analysis can better serve human well-being, and another version believes that the precautionary principle should be replaced by the ‘technical prior principle’. But they all believe that positive precautionary principle is too focused on another risk (such as environmental degradation) compared to a risk (such as the loss of potential revenue from refusing technology). However, the precautionary principle does not require relative government regulatory risk than giving priority to new technology-related risks; the precautionary principle applies to both risks. The criticized 1988 Wingspread Statement requires policymakers to consider various policy options, including the risk of inaction causing loss of potential benefits. In addition, if the prohibition of potentially beneficial technology threatens human health, the precautionary measures themselves will apply the precautionary principle.
Incoherence and superfluity objections are often used against strong positive precautionary principle. Sustein criticizes a hypothetical precautionary principle that requires human society to abandon activities that may threaten health, regardless of the cost of the preventive measures and the likelihood that the damage will occur. Sustein believes that it will be illogical to oppose both actions and inactions (such as emissions from greenhouse gases and emissions reductions).
Reducing the scope of the precautionary principle cannot avoid this paradox. Even the anti-disaster principle will oppose all action plans in certain circumstances, which makes it illogical. One response to this is that precautions should be taken only when the standard cost benefit analysis is met. However, this response is not sufficient. If the precautionary principle points to a standard cost benefit analysis, why not directly apply the standard cost benefit analysis? The two should be reasonably distinguished.
The ultimate and most important objection is that gene editing brings serious and unpredictable risks that should be ruled out by the precautionary principle. This part focuses on the role of precautionary principles in the evaluation of gene editing ethics.
And the two main conclusions drawn above are that gene editing is not completely banned in any reasonable form of precautionary principle; the precautionary principle can help to form the gene editing development trajectory by encouraging some of the genome editing applications. Indeed, the negative precautionary principle does not prescribe any specific method for weighing the possible costs and benefits of gene editing. This article considers that only moderately positive precautionary principle can provide useful guidance for decision-making.
According to the difference of intervention target cells, human gene editing can be divided into somatic cell gene editing and germline cell gene editing. Somatic gene editing technology only interferes with human somatic cells. This intervention is not integrated into the chromosomes of the recipient cell; so that the change of the subject’s genetic information is limited to the lifetime of the subject and will not be passed on to offspring. Somatic gene editing is also called non-genetic gene editing. Germline cell gene editing is the genetic intervention of human gametes, fertilized eggs or embryos by replacing the genetic genes in the germ cells changing the pathological genetic material in the germ cells, so as to eradicate the genetic diseases, or through genetic improvement the purpose of enhancing human traits. Germline gene editing is also called genetic editing. Gene-edited babies not only include genetic screening for eugenics through pre-implantation genetic diagnosis, and tissue matching for the treatment of children with genetic diseases, but also including genetic improvement aimed at enhancing human traits.
When it comes to He Jiankui’s experiments, at present, scientists mainly use CRISPR/Cas9 technology for human gene editing. This technology has always been known for its simplicity, high efficiency and low price. There are also some clinical applications. However, from the perspective of science and technology, whether it is the CRISPR/Cas9 technology itself or He Jiankui’s experiments there are varying degrees of defects. The prerequisite for a technology to be tested in humans is that sufficient scientific evidence has been obtained through a large number of studies and experiments to prove that there is no obvious harm to animals, and the consent of the subjects has been obtained. This is not only based on a rigorous and responsible scientific research attitude, but also a basic requirement based on safeguarding the rights of subjects. For the purpose of biological science research, human testing is a subject that cannot be bypassed, and it is also the last step of research. The first priority of medicine is not to hurt, and the second is treatment. However, if a technology is not yet mature enough to be applied to humans, it will bring many unknown risks to humans. Judging from the current research status of gene editing CRISPR/Cas9 technology worldwide, this technology is not yet mature enough to put gene-edited human embryos into the uterus and cultivate adults.
Many experts have doubts about the necessity of human trials of gene editing technology. The human gene editing done by He Jiankui only removes a single gene in the human body. The technical threshold is low. It does not involve complicated problems such as difficulty in targeting and removal of multiple genes. The application of this technology is essentially not novel. Sex and originality, scientists also bluntly said that this technique could be done by biology undergraduates. In addition, studies have shown that about 1 percent of people in the world lack the CCR5 gene and the HIV virus lacks receptors, so these people are lucky to be born immune to the HIV virus. However, it should be aware that CCR5 gene is only a receptor for HIV infection. The HIV virus changes in various forms. The lack of CCR5 gene can only avoid a certain form of HIV virus infestation and cannot be completely immune to HIV. Therefore, He Jiankui’s elimination of the CCR5 gene in the human body does not necessarily achieve the noble result of creating a perfect human.
Given the rapid development of biotechnology, the regulatory framework of the coordination framework is impractical in Chinese Mainland. First, the current system lacks the ability to be fully supervised, and new products created by CRISPR may not meet the current outdated legal definition. Second, the current system involves a large number of government agencies, staggered functions, confusion for developers, increased research and development costs passed on to consumers. Third, the intertwining of the supervisory bodies in the current system leads to unnecessary delays, the need to identify appropriate product review bodies, the inefficiency and the ease of resetting the entire process. Finally, after the coordination framework, the coordination framework is too focused on the final product, ignoring the process of creating these products that harm the public interest.
As a result, the framework for coordination is outdated and there is an urgent need for radical reforms to address the unique issues associated with 21st Century gene editing products. Allowing the gene editing market to adjust itself will exacerbate ethical and national security issues, and the complete ban on CRISPR, which may have a positive effect on human health, is also undesirable. Therefore, the best way is to standardize the use of CRISPR technology.
The reasons why human reproductive system editors need global regulatory initiatives are as follows: first, the human genome is shared by all human beings, and the results and impacts of the application of genealogy editing will not and cannot be limited to any country or region, and the medical risks, social problems, threats to human rights and human dignity caused by it should also be shared by all human beings. Second, the failure of gene editing in the reproductive system will bring medical risks. Chimerism will lead to serious health risks and other miss-target effects in the subsequent development stage, which cannot be excluded by pre-implantation genetic diagnosis; at the same time, there are also many unpredictable effects on future generations. Thirdly, even if the genealogy editing is successful, there will be many ethical problems: based on the ‘landslide theory’, gene enhancement may bring a series of social impacts including eugenics; the unnatural nature of genealogy editing is ‘playing with God’; the consensus of future generations cannot be obtained. Fourth, scientists have called for the suspension of clinical application of gene editing in human reproductive system before a ‘broad social consensus’ is reached, and solving relevant governance issues will help to reach this consensus. Fifthly, gene editing technologies such as CRISPR have been able to make human reproductive system editing a reality, and effective supervision has become an urgent need.
Some basic ideas are repeated in many existing international documents and comments, including the existence of ‘road social consensus’, the assessment of risks and benefits, and international cooperation in establishing rules and guidance framework. The following will attempt to enrich the most important elements that should be included in the framework of international governance. First, the search for broad social consensus. The governance framework should include guidelines for reaching social consensus, including informing the public, measuring social consensus, determining the time-line for checking the level of ‘consent’ (i.e. social consensus), and determining the steps to be taken according to the consensus level. This social consensus not only reflects the acceptability of genealogy editing, but also distinguishes between acceptable and unacceptable human reproductive editing applications. Second, establish the distinction between acceptable and unacceptable applications. One of them may be the distinction between prevention, therapeutic application and gene augmentation program, but the complexity of disease prevention makes this distinction difficult. At the same time, the relevant social consensus, moral cognition and technological development of acceptability are not unchangeable. The governance framework should establish the method of demarcation line and strictly ensure the external boundary of acceptable application. Third, establish the preconditions of experiment and clinical trial. Given the safety and effectiveness of technology, the international governance framework should recommend prerequisites for clinical trials to ensure that research is conducted responsibly within the framework of previous social consensus. Fourth, research and clinical application management system and approval process. For the clinical application of reproductive system editors, the international governance framework should provide sufficient supervision, specify the necessary regulatory level in detail, and establish a sound regulatory system to provide reference for other countries to guide the research to be carried out responsibly. Finally, the establishment of an international coordinating body. It can assess broad social consensus, provide comprehensive and objective information to countries on a regular basis, provide recommendations on best practices, promote global dialogue, continuously assess and improve the framework of international governance, and act as a neutral body to prevent technological competition among countries. In summary, the international governance framework established through the global dialogue will ensure that the application of potentially dangerous technologies does not bring about confusing and dangerous ethical and medical problems, but is carried out responsibly and ultimately benefits all mankind.
While making progress in technology, human society must be soberly aware that the research and application of Chinese gene editing technology are still in a relatively disorderly state. As a key technology, gene editing involves many fields. The Chinese government should legislate as soon as possible to clarify the scope and prohibition of gene editing technology, set strict boundaries, encourage legal and orderly research and application, and promote the benign nature of gene editing technology. First of all, it is recommended to develop a special ‘human gene editing method’ to establish a legal system for human genetic editing, and to build a comprehensive protection system that ‘effectively supervises technology, effectively coordinates rights, and effectively promotes innovation.’ Secondly, it is clear at the conceptual level that the purpose of human genetic editing legislation is to promote the quality of human society and the realization of human welfare as the fundamental purpose; to establish the basic principles followed by human genetic editing, that is, the principle of prudence and appropriateness, the principle of transparent disclosure, respect for the principle of individual life, negative scientific principles of responsibility, principles of fairness, principles of international mutual cooperation and cooperation.
The specific regulatory recommendations presented in this paper focus on creating a single entry point for biotechnology products and creating a licensing committee for human embryo research under the National Health Commission. The most important component of this upgraded biotechnology regulatory system is the establishment of a single entry point for all CRISPR-based product applications, which will reduce the legal cost of drug development, increase the efficiency of biotechnology application processes, and have broad applicability. This article proposes to establish a central committee in Beijing as a ‘single entry point’ for the gatekeeper, composed of ethicists, scientists, regulators and legislators in different fields, with scientific knowledge, ethical knowledge and regulatory knowledge. A single access point sorting function will also allow for targeted monitoring, and regulators can appropriately expand or reduce regulation based on the novelty of the research.
In addition, a ‘single entry point’ makes it easier for regulators to move to a process-oriented regulatory system, which is critical for establishing a cross-sectional regulatory program for CRISPR research involving human embryos. Given the enormous potential of CRISPR to save lives and the possible misuse and abuse of human embryos in research, any researcher who wants to develop human embryo therapy using CRISPR technology during the research process must first report to the Licensing Committee (a specialized assessment involving human embryos). The committee that submitted the proposal submits the application and should involve the regulatory body during the product development phase. The Chinese government should adopt the same licensing system as Belgium, covering all proposed human embryo research to ensure it meets ethical standards.
Throughout Chinese existing laws and regulations, there is still room for refinement and interpretation of human gene editing supervision. From the perspective of basic principles, human gene editing laws and regulations should include the principles of respect for human dignity and human health, strict supervision principles, and the principle of equal emphasis on humanistic care and technological development. The protection of human safety should be put first. At the same time, the legislative process should follow the principles of democratization, scientific and transparent, and should be conducted on the basis of fully collecting public opinion. Experts in the field of genetic research should also be invited to evaluate and discuss the content of laws and regulations, and the legislative procedures should be reviewed. The contents of laws and regulations should be made public. Moreover, in order to prevent the government and scientific research institutions from misusing the technology, the transparency of technology application should be enhanced.
From the perspective of specific rules, the laws should respond to the problems in Chinese laws and regulations reflected in the gene-edited infant incident: (1) Strengthen the supervision of clinical trials of human gene editing technology, and refine the supervision of the ethics review committee. On the one hand, it is necessary to refine the ex-ante supervision. The ethics committee should not only review in written documents, but also conduct in-depth research within the scientific research institution, and then draw the review conclusion; on the other hand, it must improve the ex-post supervision and carry out long-term continuous ethical supervision. It should prevent situations in which subsequent actions deviate from ethical purposes. In addition, it is necessary to build a monitoring system for the ethics review committee, and the powers need to be restricted by laws. According to the provisions of chapter 5 of the Procedures for Ethical Review of Biomedical Research in Humans, the National Health Commission of the People’s Republic of China and local health administrative departments are mainly responsible for supervising the ethical review of biomedical research involving people. (2) Clarify the restricted areas of human gene editing technology. First of all, it can be clarified in the legislation that when patients on the verge of death cannot be treated by other methods, with the consent of the patient or the consent of the close relatives of the patient who has no intention of expressing ability, the medical institution authorized by the state will perform therapeutic human gene editing on it. Essentially, human gene editing is used as a medical method, and it can only be applied in distress situations. The definition of distress here still needs to be legislated in conjunction with the medical field. Secondly, gene editing on human embryos can only be used for scientific research, and should follow international treaties and be destroyed within 14 days of embryo development. Except for the situations described above, no one or any institution can perform anything on normal humans. In the form of gene editing, gene-edited human embryos cannot be implanted into humans or other animals. Finally, the legislation should distinguish between gene editing for somatic cells and germ cells. The latter is completely prohibited except for serious harm to human health, while the former can be recognized by the patient or the close relatives of those who have no intention to express the ability. (3) It is not only necessary to clarify its status and civil liability from the civil code system, but also to formulate amendments to the criminal regulations to penalize violations of laws and regulations, violations of human dignity and health, and regulate the penalties imposed on them, such as setting fixed-term imprisonment, life imprisonment, and additional penalties. (4) Improve the protection of subjects’ rights and enhance the humanistic care in science. This not only needs to accelerate the establishment of genetic equality and privacy protection from the social level, but also needs a sound legal system to protect it. The key to the legal protection of an emerging right is to establish the liability of the right. The civil and criminal litigation regulations should be updated in a timely manner, and there should be more cases where subjects can initiate civil tort litigation and criminal litigation for situations where their rights are violated. In response to genetic discrimination, on the one hand, the constitutional equality principle should be implemented in the employment field, and punitive measures should be established in the field of labor law for companies that implement genetic discrimination; at the same time, the courts should strengthen the review of individual cases of discrimination and clarify the definition and scope of discrimination to protect citizens’ equal rights. On the other hand, the Chinese legal system does not provide genetic personality rights, but in a sense, the construction of genetic personality rights theory can emphasize the protection of human dignity and strengthen society’s attention to genetic personality, which may effectively avoid genes and the occurrence of discrimination and similar phenomena. Regarding privacy protection, the personal information of gene-edited humans can be more comprehensively protected from the perspective of big data legislation, etc. This is also to prevent genetic discrimination and subsequent social problems from occurring.
In contrast progressive technology, the laws and regulations on gene editing technology are imperfect in Chinese Mainland, and global standardization has not yet been achieved. These regulations hinder the government’s ability to effectively monitor CRISPR technology. This article proposes a new biotechnology regulatory system that focuses on the process of using CRISPR to create products rather than the product itself, with a focus on using human embryos for ethical research to maximize the potential benefits of CRISPR.
In the emerging science and technology, the part that is beneficial to mankind must be legalized and guided through legislation. At the same time, the abuse of new technology must be regulated by laws. Improper use of technology should be restricted or prohibited, but the laws cannot be a tool to stifle new technology and social development, but should become an institutional engine that regulates and leads the development of emerging science and technology. This is another value dimension that needs to be paid attention to in the future legal regulation of human gene editing technology.
