A new and cheap gene-editing technique has brought the possibility of the genetic manipulation of human reproductive cells closer than ever before.
The technique is called CRISPR/Cas9. It’s quick, easy, accurate, and comes at the low price of $30 USD. CRISPRs (clustered regularly interspaced short palindromic repeat sequences) are parts of the immune systems of simple lifeforms like bacteria. When viruses attack bacterial cells, CRISPRs send RNA (ribonucleic acid) molecules and an enzyme called Cas9 to destroy the virus’s genome by cutting it apart. The DNA (deoxyribonucleic acid) from the virus is then stored within the CRISPRs so they can remember how to attack the virus, essentially creating a genetic filofax of past and future enemies. This process renders the virus unable to reproduce and stops the infection process in its tracks. Essentially hacking the CRISPR system, biologists Jennifer Doudna and Emmanuelle Charpentier established that RNA encoded with a particular DNA ‘address’ could lead the RNA directly to a speci fic place in a cell. Once there, the Cas9 enzyme would either destroy the target DNA, or replace it with another gene. Charpentier says that during the experimentation and development process, “it struck us that this could be a very powerful tool for manipulating genes… Suddenly, we realised the importance of our discovery.” An important discovery indeed, when you consider some of the applications of the technique. Because genes are responsible for sending instructions to other parts of your body, changing the structure of genes changes the contents of those instructions. At a basic level, the CRISPR/Cas9 technique allows speci fic genes to be manipulated. This means we can pinpoint the function of certain genes based on the outcome of these manipulations. Level up and this technology allows for the more precise study of genetic disease using animal models.
Gene editing has the potential to cure many diseases, but is it being researched in an ethical manner?
A recent paper published in Science reported the successful use of CRISPR/Cas9 to treat Duchenne muscular dystrophy in adult mice by cutting out the defective gene. It’s no surprise really that CRISPR/Cas9 was awarded the Science 2015 Breakthrough of the Year, and Doudna and Charpentier are pegged for a 2016 Nobel prize. But, in the immortal words of Uncle Ben (RIP), ‘With great power comes great responsibility’. In studies like the one mentioned above, the modi fied genes could not be passed on to offspring because they aren’t present in reproductive cells (the germ line). Editing the germ line means that when the cell replicates it creates more versions of its mutated form. In the case of reproduction, the o ffspring then inherit the mutant gene. Bioscientist and Chairman of the Alliance for Regenerative Medicine, Edward Lanphier (along with a bevy of equally powerful co-authors) published a commentary on the issue in Nature stating: “Genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable.” Of course, someone did it anyway. A team of researchers removed part of the gene responsible for a genetic blood condition (beta thalassemia), and implanted the modified DNA into non-viable human embryos (IVF cast-offs). The technique was only moderately successful, with a small number of the modified cells surviving. The paper was rejected by Nature and Science journal because of ethical concerns, and described as “a landmark, as well as a cautionary tale” by Harvard biologist George Daley, who also advised that “their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes”. Nonetheless, recent findings have emerged demonstrating that a small number of fertilised human eggs (again, IVF cast-o ffs) were successfully modi fied with a mutation that prevents HIV infection. Daley weighed in again, stating, “the science is going forward before there’s been the general consensus after deliberation that such an approach is medically warranted.” And while promises like the eradication of HIV are understandably exciting, there is also evidence that some virus cells can evade the CRISPR o ffense, and continue to reproduce the diseased version of themselves, while simultaneously becoming immune to future CRISPR attacks. Quite the rebound e ffect. While technically in its infancy, the field of germ line modi fication is expanding at a rate of knots. Without caution, the implications of these developments might not be realised for many generations, and their vast therapeutic potential overlooked in favour of scienti fically validated eugenics. Dr Jessica L Paterson, Senior Research Fellow, CQUniversity, Appleton Institute @drjesspaterson