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Controversies in genetic editing

Advances in medical treatments using CRISPR gene editing demand the establishment of governance mechanisms to guarantee equal access

Helena Leopardi

Are gene-editing technologies being developed faster than they can be regulated? With this question on the horizon, geneticists, biologists, bioethicists, and legal scholars have been preparing to support global regulation for the use of tools such as CRISPR, which uses proteins to cut DNA and make changes to specific parts of genes. They have also been highlighting the need to establish governance mechanisms that give citizens equal access to scientific advances that could even cure rare diseases, including spinal muscular atrophy (SMA) which in severe cases can be fatal within the first two years of life.

The development of CRISPR (an acronym for clustered regularly interspaced short palindromic repeats) earned French geneticist Emmanuelle Charpentier and American biochemist Jennifer Doudna the 2020 Nobel Prize in Chemistry. In 2012, they worked together to come up with a faster and more accessible gene-editing system (see Pesquisa FAPESP issue nº 288). Despite the scientific and technological progress made in the area, scientists interviewed for this article note that there is a legislative vacuum when it comes to genetic editing techniques, including CRISPR, stressing that establishing a dialogue with scholars from the human and social sciences could help overcome this international challenge.

The bioethical debate surrounding CRISPR gained momentum in 2018, when Chinese biophysicist He Jiankui of the Southern University of Science and Technology in Shenzhen edited the embryos of a set of healthy female twins to make them immune to the HIV virus (see Pesquisa FAPESP issue nº 274). The experiment caused apprehension in the scientific community regarding the extent to which we should interfere with the genome of future generations. “It broke one of the most important ethical barriers of our time: genetic alteration of an embryo—the human germline—a boundary beyond which we do not have enough knowledge or civilizational maturity to deal with,” argues Norton Nohama, a bioethicist from the Pontifical Catholic University of Paraná (PUC-PR). According to the researcher, technological advances have resulted in the need for scientists to discuss issues that once seemed so distant that some considered the debate unnecessary.

In the wake of this progress, the World Health Organization (WHO) published its first recommendations on research related to human genome editing in 2021. Titled “Human genome editing: recommendations,” “Human genome editing: a framework for governance,” and “Human genome editing: position paper,” the documents took two years to write and include contributions from scientists, patients, religious leaders, and Indigenous peoples. They state that human genome editing techniques should function as tools to foster the development of public health and therapies for genetic diseases for which there is currently no treatment. Containing nine recommendations, the guidelines also advise that clinical trials involving human genome editing technologies should be reviewed and approved by ethics committees before their inclusion in national and regional databases and that these records contain keywords that ensure they are correctly identified. Furthermore, genome editing should only be carried out in locations where there are bodies capable of supervising the research.

As part of global concerns about human genome editing, researchers from PUC-PR are preparing to launch a book in January 2023 that outlines the ethical issues related to CRISPR and the challenges of regulation. Nohama, who is one of the book’s authors, explains that studies on recombinant DNA and transgenics led to the development of biosafety regulations by Brazil’s National Biosafety Technical Commission (CTNBIO), an agency linked to the Ministry of Science, Technology, and Innovation. Techniques such as CRISPR are known as Innovative Precision Improvement Technologies (IPITs). “Recombinant DNA tools take pieces of DNA from one species and put them into another, allowing Genetically Modified Organisms [GMOs] to be created. CRISPR, on the other hand, performs a similar procedure with the organism’s own DNA,” explains Nohama. According to him, the European Union understands that CRISPR needs to be regulated in a similar way to GMOs. Alexandre Nepomuceno, current head of the Soy Division of the Brazilian Agricultural Research Corporation (EMBRAPA), is a biotechnology expert recently appointed to his 9th term at CTNBio by the Ministry of Agriculture. He explains that in Brazil, Resolution 16 of 2018 establishes a set of requirements for presenting and consulting on IPITs, providing a form of biosafety analysis mechanism. “Through this resolution, CTNBio analyzes studies and products developed using gene-editing techniques on a case-by-case basis, including those that use CRISPR. The Brazilian biosafety commission assesses whether the final product will be considered a conventional organism, which could equally have been obtained by other techniques, such as traditional breeding, for example, or whether it contains DNA from another species, in which case it is considered transgenic.” The agronomist also highlights Law 11.105/05, which establishes safety standards and inspection mechanisms for the production, manipulation, storage, and study of genetically modified organisms and authorizes CTNBio to draft regulations that allow Brazil to maintain its biosafety and monitor technological developments in the field of biotechnology.

Helena Leopardi

Daiane Priscila Simão, a geneticist at Cilla Tech Park and another author of the work in press, explains that research with CRISPR requires authorization from Brazil’s National Research Ethics Commission (CONEP), which is responsible for determining whether the study’s benefits outweigh any possible risks. “Due to the complexity of the debate and the fact that little is known about the long-term consequences, the process tends to be slow, which affects the progress of scientific studies,” he says. Spanish biologist Arcadi Navarro i Cuartiellas of the Autonomous University of Barcelona and the Pompeu Fabra University, both in Spain, agrees that some regulatory frameworks could present obstacles to scientific and clinical advances. He highlights that Article 27 of the United Nations (UN) Universal Declaration of Human Rights, issued in 1948 and ratified by 169 countries, establishes that people have the right to benefit from advances in science. This idea, however, is often in conflict with moral arguments. “There is potential for CRISPR to be used in eugenic applications, such as to create supposedly more beautiful and intelligent babies, but on the other hand it enables the creation of therapies for serious illnesses that until recently were incurable. It would be irresponsible not to invest in its development,” claims the biologist, who is also the director of the Center for Genomic Regulation at the Pasqual Maragall Foundation. If scientific advances can have both negative and positive applications, legislation must be developed to prevent or limit misuse of the technique, he says.

Although genetic interventions in the germline and embryos is prohibited in Brazil, Mayana Zatz, a molecular biologist and geneticist from the Biosciences Institute of the University of São Paulo (USP) and head of the Human Genome Research Center, one of the of Research, Innovation, and Dissemination Centers funded by FAPESP, defends the importance of research involving embryos that will not be implanted. It is the only way, for example, to discover how to correct malignant mutations in the embryo and in future generations, she explains. According to the geneticist, one of the most advanced areas of research in this field, not just in Brazil but also in the USA, is the use of pig organs in humans. “The human genome is 98% the same as the pig’s, but there are genes from the animal that can cause acute rejection when transplanting its organs into a human,” she says. By using CRISPR technology, she explains, it is possible to identify and silence the genes responsible for this rejection. “We have already produced pig embryos with silenced genes and the next step is to implant them into a sow so that she will have offspring that will serve as potential organ donors for humans. This next phase is dependent on close dialogue with local ethics committees and CONEP,” she reports. Zatz believes the biggest dilemma with genetic editing is that it can have unforeseen consequences in the long term. One of the risks is random alteration of genes other than the one with the mutation. She thus cites the need for the scientific community to follow the situation of the Chinese twins born in 2018, to measure any possible problems involving the changes made to their genomes.

Nohama argues that the regulatory challenges currently faced can gain insight from an emerging field of bioethics that focuses on dealing with the future as an object of analysis. “Classic schools of bioethical thought treat the present as an object of study,” he explains. This is the case with utilitarianism and protectionist bioethics, he says. The former seeks to ensure that scientific advances reach the greatest number of people and has been the basis for decisions by health service managers; the latter aims to equalize conflicts of interest between more and less economically favored populations. According to Nohama, traditional schools of thought place the individual at the center of their reflections. “It turns out that environmental interests, for example, are not the same as human interests. When we place the environment at the center of the discussion, priorities change and the concept of scientific progress may no longer be in the foreground,” he highlights.

For this reason, argues Nohama, the ethical debate surrounding CRISPR must include the future as an object of study. To encourage this discussion, he cites the work of German philosopher Han Jonas (1903–1993), who has guided contemplations on the impact of gene-editing therapies on the future of humanity. One of the founders of a philosophy known as the bioethics of responsibility, his studies focus on models of progress. Nohama highlights that the current model of scientific production is fragmented, meaning that gene-editing advances are analyzed from a technical perspective, while their bioethical implications are relegated to the background. “Due to this separation, the problems and consequences of scientific advances are seen as transitory concerns exclusive to the technique, on which it is not pertinent to make a value judgment,” he explains. “Tools like CRISPR involve risks shared by all of humanity. However, its benefits may not be shared equally among everyone,” says Nohama. The bioethicist mentions a survey in the journal Nature indicating that between 2013 and 2015, US$600 million was invested in CRISPR research worldwide. The same study showed that patent applications related to the technique have been on the rise over the last eight years. In 2014 alone, the Massachusetts Institute of Technology (MIT) filed 62 related patent applications, the Broad Institute 57, and American agricultural company Dow Agrosciences filed 28. None involved patents in the public domain. “How can we guarantee equality and universal access to the products that result from these new biotechnologies if they are appropriated by an economy of power and their global reach is based on industrial and intellectual property whose only objective is profit?” asks the PUC-PR researcher.

Zatz explains that CRISPR-based treatments for sickle-cell anemia, which is caused by a genetic mutation that leads to the deformation of red blood cells, can cost as much as US$1 million per patient—but the disease is prevalent in Africa, a less economically privileged region. “Many treatments for rare genetic diseases have an exorbitant cost. For example, a new gene therapy for SMA costs $2.1 million. The cost is enormous because the companies that invested in the research want to make a profit, and since the diseases are relatively rare, the number of potential patients is relatively small,” she says.

The treatment is expensive, among other reasons, because it involves removing stem cells from patients, editing them, and then reinserting them back into the body. With the aim of resolving this type of dilemma, Zatz notes, bioethics is one of the central axes of this year’s Human Genome Editing Summit, an event organized by the UK Academy of Medical Sciences, the US National Academies of Sciences, Engineering, and Medicine, and the World Academy of Sciences that will be held in the UK in March 2023.

Scientific articles
NOHAMA, N. et al. O impacto ambiental da edição genética no Brasil. Temáticas: Processos, conflitos e desafios: As questões ambientais pela perspectiva das ciências sociais. vol. 29, no. 5, 2021.

ROSANELI, C. F. & FISCHER, M. L. Bioética, saúde global e meio ambiente. Série bioética. vol. 14. Curitiba: Editora CRV.
NOHAMA, N. et al. CRISPR e edição genômica: Técnica, bioética e controvérsias. Ponta Grossa: Atena Editora. In press.

Human genome editing: A framework for governance. World Health Organization. 2021.
Human genome editing: Position paper. World Health Organization; 2021.