SHRUTI SHARMA
Gene editing is the deliberate insertion, deletion, or replacement of a DNA sequence in the genome of a living cell. Scientists have been able to edit genes for many years. But the discovery of a tool known as CRISPR/Cas9 has revolutionized the field.
HOW DOES CRISPR/CAS9 WORK?
CRISPR works like the search function in Microsoft Word, to find specific sequences of genetic code. Cas9 is an enzyme that then cuts and deletes the targeted code. Scientists then insert new code, to replace what has been deleted.
In more scientific terms, CRISPR/Cas9 is made up of two parts: CRISPR, a stretch of bacterial DNA, and CRISPR-associated protein 9 (Cas9). Together, this tandem works as a manmade version of a natural defense mechanism, used by bacteria and other single-celled microorganisms to fight off invading viruses by chopping up their DNA.
Shruti Sharma is a research analyst with the Technology and International Affairs Program at the Carnegie Endowment for International Peace. She works primarily on the safety, security, and ethical implications of emerging biotechnologies.
CRISPR recognizes the target gene and guides the Cas9 protein, which then precisely slices the target DNA in a specific spot. Once the DNA is cut, researchers use the cell’s DNA repair function to add or delete genes, or to replace the existing segment with a customized DNA sequence.
HOW IS GENE EDITING TECHNOLOGY BEING USED AROUND THE WORLD?
Gene editing has the potential to alter any DNA sequence, whether in bacteria, plants, animals, or humans, so – in theory, if not yet in practice – it has a virtually limitless range of possible applications in living organisms.
Plant geneticists all over the world have been experimenting with gene editing to improve the yield and nutritional value of crops, as well as to boost their resistance to disease and drought. For example, the seed company DuPont Pioneer is working with a biotechnology firm called Caribou Biosciences to develop a high-yield strain of CRISPR-edited corn.
There is also immense potential to produce gene-edited animals. U.S. scientists are trying to find out whether and how gene editing can be used to breed cattle that cope better with heat and humidity. Meanwhile, researchers at the University of Edinburgh’s Roslin Institute are seeking to use CRISPR/Cas9 to rear pigs that are resistant to a debilitating viral disease.
Other scientists are trying to use gene editing to make mosquitos more resistant to malarial parasites. This could curb mosquito-borne illnesses like malaria, or even wipe out the disease-carrying mosquito population.
Researchers are also examining how gene editing might treat human single-gene disorders like sickle cell anemia, cystic fibrosis, and hemophilia. Eventually, CRISPR may help doctors treat and prevent more complicated diseases, such as cancer, heart disease, human immunodeficiency virus (HIV) infection, and mental illnesses such as schizophrenia, bipolar disorder, and depression.
WHY IS GENE EDITING SO CONTROVERSIAL?
So far, gene editing has mostly been used on non-reproductive cells to try to cure human diseases. This kind of gene therapy has targeted effects on specific organs, which are not passed down to future generations.
But some genetic changes would have more far-reaching effects. Editing the human germline—making changes to reproductive cells such as eggs, sperm, and embryos—entails changes to heritable DNA. What makes it so controversial is its power to change the resulting child’s genetic makeup permanently—and that of his or her descendants. There are also fears that such gene editing may be used for nontherapeutic purposes or genetic enhancement – “designer babies”.
Such interventions raise serious safety concerns. One risk is off-target effects: the editing tool might miss the target gene and affect another similar sequence, with harmful unintended consequences. Another serious risk is mosaicism. This arises when gene editing fails to edit the DNA of all relevant cells, so the embryo inherits a mixture of edited and unedited cells. This could leave any resulting child vulnerable to the genetic disease that the editing was supposed to prevent.
The limited safety and efficacy studies of gene editing on human embryos in vitro has brought this technology’s incredible potential and pitfalls into sharp contrast.
WHAT DO INDIAN CONSUMERS AND OFFICIALS THINK ABOUT GENE EDITING?
Many Indian consumers worry about the possible negative health effects of consuming genetically modified (GM) foods, which have had foreign DNA added to their genomes. Although these fears have not been validated by any scientific study, there has been a deep resistance to GM crops in India.
Plant geneticists are looking into how they could use CRISPR/Cas9 to make staple Indian crops, such as bananas and wheat, more nutritious. Unlike traditional GM techniques, CRISPR only involves changes to a plant’s existing DNA. But this may not convince Indian consumers, so a lack of scientific communication and misinformation might stifle the development of CRISPR crops.
Many Indian researchers are already working on gene editing and how it could be used in the healthcare sector. Several research laboratories in India have started experimenting with the use of CRISPR/Cas9 to treat blood disorders, like sickle cell anemia and beta-thalassemia, by carrying out preclinical studies that involve isolating embryonic stem cells.
In 2014, the Indian government’s Department of Biotechnology set up a task force on genome engineering technologies and their applications to promote development in the field.
Indian companies are also investing in the development and commercialization of gene-edited products. But private companies’ contributions have been limited by the long gestation periods before products are ready to sell, bureaucratic delays related to product approval, and India’s multilayered regulatory structures.
ARE THERE FEARS IN INDIA ABOUT MORE HIGH-RISK USES OR THE POTENTIAL MISUSE OF GENE EDITING?
The healthcare-oriented wing of the Rashtriya Swayamsevak Sangh, a Hindu nationalist group, announced in 2017 a plan that it claims would produce fair-skinned, smart, customized babies.
This particular project calls for the use of Ayurvedic herbs, not CRISPR technology. But whether or not such a method were effective, it is emblematic of the temptation to employ advances in medicine in ways that raise ethical quandaries and could have profound unintended consequences.
Given many Indian parents’ historical preference for boys, there are fears that gene editing could be used to customize the genetic material of babies, potentially worsening the country’s imbalanced sex ratio. In such a scenario, parents could effectively choose their child’s sex before conception.
Unlike in the West, caste and religion are also major factors in India when it comes to choosing egg and sperm donors. Some fear that, if misused by the elite, gene editing has the potential to exacerbate inequalities that already exist in Indian society.
AS MAJOR COUNTRIES LIKE CHINA AND INDIA RACE TO HARNESS GENE EDITING, WILL ETHICAL AND SAFETY CONSIDERATIONS BE PUT ON THE BACK BURNER?
China and India’s political systems are fundamentally different. This affects how people in each country engage on biotechnology.
In India, most researchers rely on government grants for their research. Indian elected officials are sensitive to public opinion, so they are less likely to fund controversial experiments involving human embryonic gene editing.
The birth of the twin babies with alleged edited genomes in China last November shows the gaps in ethical and safety guidelines that can occur. Nonetheless, this controversial experiment was widely condemned in China, by the government and other scientists alike. The Chinese experiment sparked a huge debate among the broader scientific community—in China, India, and other countries as well—on establishing guidelines to regulate human gene editing research.
DO COUNTRIES HAVE DIFFERENT RULES GOVERNING HUMAN EMBRYONIC GENE EDITING, OR IS THERE AN INTERNATIONAL STANDARD OF ETHICS?
Different nations have different laws and guidelines governing human embryonic research, and such regulations reflect a nation’s culture to some extent. For example, a medical ethicist at Shanxi Medical University told the New York Times “Confucian thinking says that someone becomes a person after they are born. That is different from the United States or other countries with a Christian influence, where because of religion they may feel research on embryos is not ok.”
Some countries, like Germany and Canada, restrict research involving human embryos through laws that carry criminal penalties. Others countries have far more lax regulations. The United States, for instance, has a restrictive strategy and bans federal funding for research involving human embryos, but the government has not officially banned private endeavors from carrying out such research.
In the middle are countries like France and Australia, where research on the subject is often allowed, as long as it meets certain restrictions and does not lead to babies carried to term. In the UK, such research is managed by an independent organization, the Human Fertilization and Embryology Authority. It gave permission to a group of researchers to conduct CRISPR research on human embryos in 2016, but such experiments still need extra approval from an ethics committee.
Countries like India, China, and Japan are more permissive than the United States, and these countries have unenforceable guidelines – based on a general consensus among experts – that govern such experiments.
Yet despite the apparent discrepancy between different countries on the degree of perceived acceptability of embryo research, several leading scientists and bioethicists from all over the world are calling for an international governance framework, in which countries would “voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met.” An advisory panel of the World Health Organization has also recommended an international registry to track all research into editing the human genome.
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