On November 26, 2018, the birth of a pair of babies named Lulu and Nana and gene editing not only detonated the biomedical community, but also aroused widespread public concern. He Jiankui, the scientist in charge of this scientific research work, suddenly stood on the cusp of public opinion.Compared with the question of the safety and necessity of the CRISPR-Cas9 technology used in the experiment and the CCR5 gene editing itself at the scientific level, people are more concerned about the adverse effects of the "custom baby" at the ethical level.On the one hand, the relentless label of the "experiment" will be accompanied by the two poor children for life, which is embarrassing; on the other hand, once the "custom baby" is out of reach, human society will lose its minimum fairness, and even in the future, the "human" species will be redefined and the consequences will be disastrous.
Generally speaking, ethics is a higher social norm than the standard prescribed by law.In some cases, in view of the seriousness of the problem and the operability of the law, it is reasonable and necessary to restrict human behavior by law to make it ethical and ethical.If ethics and morality require that we respect the elderly and love children, the law also stipulates obligations such as upbringing and maintenance, and urges people to follow the ethical principles of respecting the elderly and children.
Gene editing technology as a technology that can change the genetic characteristics of organisms is undoubtedly a sharp double-edged sword.In particular, when it is used for human gene editing, it involves complex ethical, ethical, and philosophical issues outside the technology. Therefore, scientists from various countries who master the technology are very cautious about the development of related research.What are the legal provisions concerning medical ethics in our country that help prevent this double-edged sword from causing irreparable damage, and what problems of the law are exposed in the He Jiankui incident? In this paper, the author will discuss this hot issue from the perspective of ethics and law.
1.Basic ethical guidelines
"Clinical trials" are medical trials conducted on human subjects and inevitably involve more complex ethical issues than other trials such as animal experiments.Internationally accepted ethical guidelines for clinical trials can be traced back to the Declaration of Helsinki of the World Medical Assembly, first published in 1964, which states that the interests of subjects in clinical trials are higher than those of science and also higher than those of society; on this basis, the declaration requires that clinical research must make a trade-off between potential risks and benefits, and that clinical trials should be stopped once it is found that the risks outweigh the benefits, and that investigators must obtain their consent with the full knowledge of the subjects.With the development of the times, the declaration has added to subsequent revisions the content of "unproven interventions in clinical practice", requiring that even if such interventions are applied, they should be based on the evaluation and design of their safety and efficacy.
The Declaration of Helsinki is only a guiding platform document, and it is not legally binding in itself. Therefore, the above ethical guidelines need to be reflected in the specific laws and regulations of various countries before they can be implemented.For example, China's "Drug Administration Law," "Drug Registration Regulations," "Pharmaceutical Clinical Trial Quality Management Standards," and other laws and regulations on the review of the ethics committee involved in clinical trials in drug development, the principle of informed consent, and the protection of subjects, etc., made provisions.
2.Related laws and regulations and the legality of the test
CRISPR-Cas9 gene editing technology is an emerging biological technology, often referred to as "gene scissors". It is not so much a process of drug use as a biological process of operation. Therefore, the aforementioned laws and regulations related to drugs are not applicable.
Specific to the genetic editing operation of human embryos in the He Jiankui incident, the current laws and regulations related to this in China mainly include:
Ethical Guiding Principles for Research on Human Embryonic Stem Cells, hereinafter referred to as "Ethical Principles for Stem Cells", effective in December 2003,
Administrative Measures for Clinical Research of Stem Cells (Trial), hereinafter referred to as "Trial Measures for Stem Cells", effective in July 2015,
Measures for Ethical Review of Biomedical Research Involving Persons, hereinafter referred to as "Measures for Ethical Review", effective in December 2016,
Measures for the Administration of Clinical Application of Medical Technology, hereinafter referred to as "Measures for the Administration of Applications", effective in November 2018.
It is worth noting that the issuing agencies of these regulations are the State Health Commission (formerly the Ministry of Health, the Health and Development Planning Commission), the former Ministry of Science and Technology, the former Food and Drug Administration and other State Council ministries and commissions, which belong to the departmental regulation level from the validity level.In other words, in the higher-ranking laws (issued by the NPC and its Standing Committee) and administrative regulations (issued by the State Council), the author has not yet identified normative documents that can be directly related to such clinical trials.As a result, the integrity of the current relevant regulations is not strong and has not received sufficient attention.
So, based on the above regulations, is the research behavior of He Jiankui and the corresponding behavior of the research institution legal?
For the conduct of research itself, Article 6 of the Principles of Stem Cell Ethics states: "Blastocysts obtained by in vitro fertilization, somatic cell nuclear transfer, unisexual replication techniques or genetic modification shall not have an in vitro culture period of more than 14 days from fertilization or nuclear transfer; human blastocysts obtained in the preceding paragraph that have been used for research shall not be implanted into the reproductive system of humans or any other animal."He Jiankui's experiment was to implant genetically modified embryos in vitro into the maternal reproductive system to give birth to two babies, apparently in violation of the aforementioned regulations.
For the qualification of research institutions, Article 7 of the "Stem Cell Trial Measures" clearly stipulates that stem cell clinical research institutions should be tertiary A hospitals.The reason why such regulations are made is because stem cell tests, including gene editing, not only generate ethical controversy, but also require far higher scientific research capacity, technical level, quality control, and risk control than general clinical trials. Therefore, higher thresholds should also be set for experimental institutions.However, according to the author's understanding, the Shenzhen Hemei Women and Children Hospital (hereinafter referred to as "Hemei Hospital") that undertakes this clinical trial is not a top-three hospital, so it also does not meet the requirements.
For the ethics committees that are in charge of ethical review in research institutes, it can be seen from the provisions of the "Ethical Review Measures" and "Stem Cell Trial Measures" that the ethics committee for stem cell clinical trials should be No less than seven people are composed of professionals in the fields of biomedicine and social sciences (ethics, law, sociology, etc.) and non-institutional society.Due to the limited information available, the author cannot judge whether the seven members of the Ethics Committee of Hemei Hospital meet the above requirements. However, Mr. Huang Huafeng, one of the members of the Network Communication Committee, is a dentist of the hospital and does not belong to the field of stem cell clinical treatment at all. This ridiculous arrangement also seems to run counter to the aforementioned requirements.Of course, as to whether the ethical committee has fulfilled the duties assigned by laws and regulations (such as Article 20 of the "Ethical Review Measures") in the ethical review, there have been many discussions and the author will not comment too much.
In addition, Article 17 of the "Stem Cell Trial Measures" stipulates that stem cell clinical research should meet the requirements of the "Quality Control Practice for Drug Clinical Trials" (ie, "GCP"), while Article 35 of the GCP clearly requires that research institutions must obtain the approval of the State Drug Administration before conducting clinical trials.However, it can be inferred from the birth of the child on November 26 that this clinical trial has actually started by the beginning of 2018, but the website of the China Clinical Trial Registry shows that the registration time of the trial is November 8, 2018, and the status is "supplementary registration".In other words, it cannot be ruled out that there is no registration or approval at the beginning of the clinical trial.Assuming that this is the case, the legitimacy of this clinical trial is even more questionable.
It is worth noting that Article 9 of the Measures for the Administration of Applications, which came into force in November this year, stipulates "prohibited technologies" and requires the development of a catalogue of prohibited technologies.Prohibited technologies include technologies that are clinically safe and ineffective, technologies that have major ethical issues, and new technologies that have not been demonstrated by clinical research. They are prohibited from being used in clinical practice.The author believes that the gene editing technology for human embryos used in this incident satisfies all of the above conditions and is fully justified as a "prohibited technology".However, since He Jiankui conducted the experiment earlier than the time when the management measures came into force, the legality of the experiment cannot be judged based on this clause according to the principle that the law does not trace back to the past.
3.The legal responsibility of the investigator and the testing institution
According to the laws and regulations listed above, this clinical trial is indeed suspected of being illegal.So what would the offender pay?
First of all, in the above laws and regulations, regarding the provisions of the punishment measures for researchers, the author only finds the following provisions in the "Ethical Review Measures":
Article 47: If a project researcher violates the provisions of these Measures and has any of the following circumstances, the local health and family planning administrative department at or above the county level shall order it to make rectification within a time limit, and may circulate a notice of criticism and warnings according to the seriousness of the circumstances; for the main responsible person and other responsible persons,Disciplinary actions shall be given according to law:
(1) The research project or research program has not been approved by the ethics committee to carry out the project research work without authorization;
(2) Serious adverse reactions or serious adverse events occurred during the research process have not been reported to the ethics committee in a timely manner;
(3) Conducting project research in violation of the relevant provisions of informed consent;
(4) Other violations of these Measures.
However, the episodes specified in the above articles mainly involve procedural matters in the research process, and do not involve judgments on the content of the research topic.In other words, once the approval of the ethics committee is obtained in the procedure and the obligation of timely reporting and informed consent is fulfilled, the researcher will not be punished according to this clause for unethical research content itself (for example, implanting genetically edited embryos into the mother). (Regarding the statement that He Jiankui did not obtain the subject's informed consent by proper means, the author will not comment on this because it has not yet been determined).
With regard to the punishment measures for research institutions, Article 46 of the Measures for Ethical Review provides as follows:
Article 46: Where a medical and health institution or its ethics committee violates the provisions of these Measures and has any of the following circumstances, the local health and family planning administrative department at or above the county level shall order it to make rectification within a prescribed time limit, and may circulate a notice of criticism and warnings according to the seriousness of the circumstances;Disciplinary actions shall be given according to law:
(1) The composition of the ethics committee and the qualifications of the committee members do not meet the requirements;
(2) The work system or operating procedures for ethical review have not been established;
(3) The review has not been conducted in accordance with the principles of ethical review and the relevant rules and regulations;
(4) The disclosure of the research project plan, personal information of the subjects, and the review opinions of the committee members;
(5) The filing has not been conducted as required;
(6) Other violations of the provisions of these Measures.
In this incident, as a research institute of Hemei Hospital, in addition to the ethical committee's membership may appear in the above (1) cases, the author based on the information currently known It is difficult to find other reasons for punishing it.In addition, the article stipulates that the punishment of research institutions is limited to ordering rectification within a time limit, circulating a notice of criticism, and warning. Whether such punishment can produce sufficient deterrence remains to be discussed.
Fortunately, as mentioned earlier, the "Measures for the Administration of Applications" that came into force just this month also allowed the author to see the development of relevant legislation, of which Article 43 stipulates that for medical institutions that carry out the clinical application of prohibited technologies or do not meet the requirements of the medical technology clinical application management regulations and carry out relevant medical technologies without authorization, local health administrative departments at or above the county level shall handle them in accordance with Article 47 of the "Regulations on the Administration of Medical Institutions". (That is, if the circumstances are serious, the person in charge of the medical institution and other directly responsible personnel shall be punished according to law.This provision obviously strengthens the punishment and can prevent the same events in the future to some extent.
For the civil and even criminal responsibilities that the offender should bear, the current regulations are not specifically detailed.For example, Article 49 of the "Measures for Ethical Review" only stipulates in general that if damage is caused to the person or property of another person, civil liability shall be borne according to law; if a crime is constituted, criminal liability shall be investigated according to law.However, the "law" mentioned here should be based on what method?The author believes that even if the completely new legal issues brought about by clinical trials of genetically modified embryos can apply certain provisions of existing laws and regulations, the cost paid by offenders may be very limited compared to the adverse consequences they bring.For example, Article 54 of the Tort Liability Law stipulates: "If a patient is harmed in the course of diagnosis and treatment, and the medical institution and its medical personnel are at fault, the medical institution shall bear the liability for compensation."In other words, the civil liability for medical damages is based on the premise that the patient is harmed in the diagnosis and treatment activities.However, assuming that the two children and their parents are fortunate enough not to have sequelae caused by genetic editing operations, or that it is technically difficult to prove the damage suffered, can He Jiankui and Hemei Hospital be exempted from tort liability?Even if the tort liability is established, such civil compensation may not match the degree of trampling on medical ethics and the adverse effects on society.
Judging from the previous analysis, the current laws and regulations have generally weak penalties for such illegal clinical trials, and there is no reasonable refinement of the way in which illegal liability is assumed. It needs further improvement.
It can be seen from the above that China has limited laws and regulations regarding medical clinical trials involving major ethical issues.Admittedly, for the statutory system, there is inevitably a lag in the formulation of laws and regulations for emerging things.The development of new technologies, including biotechnology, is changing with each passing day. How to guide the application direction of technologies through laws and regulations and standardize the application methods of technologies so that new technologies can benefit people rather than produce unpredictable adverse consequences is indeed a topic that legislators can consider.
The author has seen the evolution and progress from the newly implemented laws and regulations. On this basis, the author believes that the following points can be considered: First, the legislative work on the level of laws and administrative regulations can be considered. Second, it can be considered to explicitly prohibit the clinical application of a controversial technology through the introduction of a list of prohibited technologies. Third, the specific content of attribution and illegal punishment can also be further refined to make it more operable.
The world is so big that we cannot demand that all people be bound by ethics, fear nature, and fear life, but we can expect that in the near future, speculators will at least have laws to fear.