Nordic Life Science 1
e also mentions exciting possibilities related to
immunotherapy treatments in cancer, where immune cells are instructed to attack the patient’s tumor and metastases. “Clinical studies are already ongoing where the immune cells are modified with CRISPR to become more aggressive and resistant.” In his own research, Fredrik Wermeling and his research group at Karolinska Institutet are studying the immune defense in relation to autoimmune diseases and immunotherapy in cancer. “We are using CRISPR to inactivate genes in different cells, and hence identify how these genes are affecting different disease processes. We are doing this using pre-clinical models and patient material to try to identify new targets for pharmaceuticals to treat these diseases,” he explains. Wermeling sees great potential in how he and his colleagues are using CRISPR screening to understand how cancer cells develop resistance against different cancer treatments. When a drug is administrated to a cancer patient single cancer cells that succeed in avoiding the negative effects of the treatment will have survival advantages. “Through a classic ‘survival of the fittest’ evolution process, over time the patient is therefore developing tumors that are made of more and more cancer cells that are resistant against the pharmaceutical and eventually the tumor is not responding at all to the drug,” he says. “This is still a long way away, but to be able to use CRISPR screening to identify in what ways specific cancer cells avoid an initial effective pharmaceutical, and develop resistance, creates possibilities for highly effective combination treatments. There are conceptual similarities with the cocktail of three antiviral drugs that together effectively inhibit the life cycle of HIV, but where the virus quickly develops resistance if the patient is treated with only one drug at a time.” As with every powerful technology, the genetic scissors require regulation to avoid unethical applications. Causing changes in a germ cell or embryo, so that the change is inherited by coming generations, is far more controversial than editing the ordinary cells of a human being suffering from a genetic disorder via gene therapy. In 2018, CRISPR was for example used by the Chinese biologist He Jiankui to modify twin embryos used for IVF, resulting in the birth of two girls allegedly with alleles that would confer protection from infection by HIV. He bypassed ethical regulations and chose to use germline editing for preemptive protection, in addition, he did not show any clear evidence that the procedure was safe. Jiankui’s actions were condemned by the biological community. Another controversial aspect is the possibility of improving or refining perfectly normal human conditions with the help of CRISPR/Cas9. Perhaps adjustments in the genome might eventually lead to more intelligent, more productive or more beautiful human beings. For many years there have been laws and regulations that control the application of genetic engineering. The regulations include prohibitions on modifying the human genome in a way that allows the changes to be inherited. The Nobel Committee for Chemistry also states, “Experiments that involve humans and animals must always be reviewed and approved by ethical committees before they are carried out.” In 2017, a report from an international committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine in Washington, D.C., concluded that human embryo editing could be ethically permissible one day – but only in rare circumstances and with safeguards in place. “Those situations could be limited to couples who both have a serious genetic disease and for whom embryo editing is “really the last reasonable option” if they want to have a healthy biological child,” says committee co-chair Alta Charo, a bioethicist at the University of Wisconsin in Madison, US. NLS Edmund Loh, Principal investigator, Karolinska Institutet 42 NORDICLIFESCIENCE.ORG PHOTO FRANCESCO RIGHETTI