CRISPR on Trial: The Gene, the Experiment, and the Law

THE GENE AND THE EXPERIMENT

Genetic Engineering has been around for quite some time, with the first recombinant DNA molecule dating back to 1972 and, in the present time, being used to directly edit the genes of living organisms.

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Genetic engineering is a process that alters the genetic structure of an organism by either removing or introducing DNA or modifying existing genetic material using biotechnology to produce better organisms. Unlike traditional animal and plant breeding, which involves doing multiple crosses and then selecting for the organism with the desired characteristics, genetic engineering takes the gene directly from one organism and delivers it to the other. This is much faster, can be used to insert any genes from any organism (even ones from different domains), and prevents other undesirable genes from also being added. One such tool identified by scientists was the CRISPR-Cas9 mechanism.

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 CRISPR (read crisper) stands for “Clusters of Regularly Interspaced Short Palindromic Repeats” and Cas for “CRISPR-associated system”. These are short nucleotide sequences found in bacteria that are the same when read from both directions and are useful in protecting the bacteria from viruses, in the form of acquired immunity. The Cas9 protein acts as scissors and cuts the DNA where the abnormal virus DNA had attached, and makes a memory of it for future viral attacks.

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CRISPR Cas9 is now experimentally used in human studies to correct diseases such as cystic fibrosis; however, as of now, there are no fully approved clinical treatments, and its application remains largely confined to laboratory research. It is easily said to be one of the most promising techniques of the decade.  A gene sequence resembling the gene to be modified is made artificially. 

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He Jiankui of China used the stated technique to unethically produce genetically modified babies who were born as twins later in 2018. Mr. He confessed to having produced babies with modified genes to make them HIV immune. He Jiankui essentially carried out an ‘experiment’. He recruited couples in which the male partner was HIV-positive to serve as donors. Using CRISPR technology, he managed to disable a gene closely related to immunity and HIV infection: CCR5. This gene is expressed in the immune system as a cell membrane receptor protein (acceptor molecule) and plays a key role in letting the virus enter human cells. As a result, CCR5 antagonists or blockers are effective against HIV expression in AIDS patients -  they work by binding to this receptor and blocking the virus’s entry. Although CCR5 can only block HIV-1, its presence confers high HIV resistance to individuals, and its surface density on immune cells inversely correlates with rates of HIV-1 entry.

 

This could prove to be a solution to the problem He was working on; however, the possibility of this gene modification causing secondary effects (such as mosaicism or off-target mutations) was a concern that the modern world is still not ready for: the production of “superhumans”. The twins, often referred to as “Lulu” and “Nana”, are believed to be alive, but their identities and health status are not publicly disclosed to protect their privacy. At last, He Jiankui was sentenced to 3 years in prison for illegal medical practice under the Criminal Law of the People's Republic of China.

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THE EVOLUTION OF LAW

As genetic engineering emerges as one of the rapidly growing fields, establishing itself as both a need and concern, it gives rise to further legal boundaries that are involved, and what might be implemented or amended.

In He's case, the likely violations that arise lie in consent, transparency, human rights and dignity, and fundamental freedom.

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The ethical concerns and implications of gene editing are that it can have unpredictable effects on future generations, may cause genetic disorders as a result of mosaicism (the presence of populations of somatic cells that are genetically distinct in an organism), and raise concerns about the fate of the child produced using such technologies.

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The Universal Declaration on the Human Genome and Human Rights by UNESCO, adopted in 1997, identifies the human genome as a part of human dignity under Article 1. Further under article 10 it proclaims that no research or research applications concerning the human genome, in particular in the fields of biology, genetics and medicine, should prevail over respect for the human rights, fundamental freedoms and human dignity of individuals or, where applicable, of groups of people, which was further proclaimed under article 3 of Universal Declaration on Bioethics and Human Rights adopted in the year 2005. 

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Following He’s incident, WHO established a global multidisciplinary expert advisory committee in December 2018, to examine scientific, ethical, social and legal challenges associated with human genome editing. The committee published its first report in April 2019 outlining its mandate to develop global standards, ethical frameworks, and oversight mechanisms. Followed by a comprehensive governance framework on human genome editing (outlining ethical values, principles, and policy tools), along with Human genome editing: recommendations (specifying actionable recommendations in nine discrete areas) in July 2021.

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In India, at present, there are no known cases of unethical or illegal human germline gene-editing. However, keeping up with the growing discoveries (such as CRISPR technology) and research gene editing is regulated in India by a dual framework where ICMR’s (Indian Council of Medical Research) ethical guidelines are legally enforced by the Central Drugs Standard Control Organization (CDSCO), under the New Drugs and Clinical Trials (NDCT) Rules,2019, which derives its legislative power from the Drugs and Cosmetics Act,1940.

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However, before the 2019 changes, the National Guidelines for Stem cell Research (2017) served as India’s primary regulatory and ethical framework for stem cells and human gene-editing research, where it placed human germline gene therapy and reproductive cloning under “prohibited” list of research and also mandated that any gene-edited human embryo used in basic laboratory research could never be cultured beyond 14 days.

The 2017 guidelines lacked standalone legislative power and relied on a patchwork of older laws. However, the 2019 transition laid a statutory foundation.

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Under this, the operational laws specifically governing human gene editing are somatic gene editing, which involves altering non-reproductive cells, are legally categorized as “new drugs” and are governed under the NDCT Rules,2019. Further, any clinical trial using CRISPR or other gene-editing tools must be approved by the Gene Therapy Advisory and Evaluation Committee (GTAEC) and the CDSCO; failure to do so is treated as a statutory violation of drug trial laws, which may lead to a suspension of research licenses, blacklisting, or criminal prosecution.

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Germline editing involves the alteration of human embryos, sperm, or eggs. Because these changes can alter the human gene pool permanently, they face global restrictions. As per the ICMR guidelines, germline genome editing and reproductive cloning are placed under absolute prohibition.

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And since most human gene-editing relies on modified viruses or nanoparticles to carry the CRISPR ‘scissors’ into human cells, they are legally classified as Genetically Modified Organisms (GMOs). They are bound by the Rules for the Manufacture, Use, Import, Export and storage of Hazardous Microorganisms/ Genetically Engineered Organisms or Cells, 1989, enacted under the Environment Protection Act, 1986, where the labs must secure clearance from the Institutional BioSafety Committee (IBSC) to legally handle such materials.

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To conclude, in present genetic engineering is not governed by any unified piece of legislation globally, however it is guided through distinctive guidelines and rules internationally and nationally. He Jiankui believed that society will gradually accept gene editing as a common medical practice but, what remains to ponder is the question whether the people will acknowledge embryo gene editing as a practice in near future, and if yes how will law bind it, when there is a possibility to witness something never seen before.