Are we ready? CRISPR Advances Mean the Era of Germline Gene Editing has Arrived
Fast, accurate and easy to use, CRISPR-Cas9 has made genomic editing more efficient, but at the same time made editing of the human germline much more feasible, breaking down many of the ethical barriers erected to prevent scientists from ‘edit the genes of heredity.
“The ethical debate over what is now called human gene editing has been going on for over 50 years,” writes Dr. John H. Evans, co-director of the Institute for Practical Ethics at the University of California, San Diego. . “For most of this time, there has been a consensus that there is a moral divide between somatic and human germline editing.”
In an essay published in the Proceedings of the National Academy of Sciences (PNAS), Evans argues that many of the powerful bioethical arguments that once made germline editing a verboten concept have started to dissolve in the CRISPR era.
Evans – and a growing number of other ethicists – argue that the moral division that has long separated scientific thought about the germline and somatic cell editing is weakening noticeably.
The 2018 announcement in China by He Jianqui who genetically modified human embryos via CRISPR – producing twins known as Lulu and Nana – helped strengthen policies on germline gene editing. Despite worldwide contempt for him for carrying out a brazen act of human experimentation, his research also helped usher in a more moderate view regarding the manipulation of germline genes. Policy makers have followed with a milder tone in guidelines on the feasibility of research involving genes for inheritance. It turned out that a growing number of scientists were expressing interest in developing potential cures by manipulating genetic sequences in germline DNA.
âCurrently, despite appearances, in the dominant bioethics debate in the United States and the United Kingdom which has the greatest influence on what is really going on with science policy, the somatic / germinal distinction has lost its power. For example, despite the outcry over He Jianqui and the birth of germline modified children in China, the leadership of the Second International Summit on Human Germline Editing implicitly agreed with him that it is in principle acceptable to engage in germline intervention, as long as it is safe and the protections of human subjects are met, âEvans wrote in PNAS.
“Indeed, a commission from the National Academy of Medicine, the National Academy of Science and the Royal Society recently developed a ‘translational pathway’ for the ‘responsible use’ of germline applications,” Evans argued.
Genome editing actually refers to several technologies that allow scientists to ârewriteâ segments of an organism’s genetic code. DNA sequences can be deleted, or receive additions or be modified at virtually any genomic location. Unlike other genome editing technologies, CRISPR-Cas9 is faster, more efficient and easier to use. And CRISPR, more and more biologists say, has opened up a new frontier of possibilities in what can be achieved with a powerful biological tool.
But as high-tech as CRISPR may seem, it was not invented in the laboratory. The editing technique is actually an adaptation of a natural genome editing system found in bacteria and archaea. These organisms literally grab infinitesimal sequences of genetic material from the viruses that invade them, then use those captured sequences to create segments of DNA called CRISPR chips.
The networks allow bacteria and archaea to call back viral infiltrators if they invade in the future. When the viruses – the bacteriophages – attack again, the bacteria or archaea produce RNA from the CRISPR chips to focus on the viral genes. The bacteria and archaea then rely on Cas9 to chop the viral genes, which effectively destroys the virus. In many ways, this ability to remember infectious viruses is tantamount to a raw immune system, acting similarly to the memory B and T cells of the much more sophisticated mammalian immune system.
Jennifer Doudna from the University of California at Berkeley and Emmanuelle Charpentier from the Institut Pasteur in Paris won the 2020 Nobel Prize in Chemistry for their collaborative work involving CRISPR-Cas9. The technology was originally developed – and named – by Spanish biologist Francis Mojica, a professor at the University of Alicante in Spain. He was not included as a recipient of the award.
Evans, meanwhile, points out that by the time CRISPR became a powerful laboratory tool in the early 2010s, it still seemed like “germline modification was always going to be impossible.”
âAfter it became clear that some scientists were trying to use CRISPR to modify human embryos in the lab,â Evans wrote, âmany scientific groups have published position papers on human germline editing, mainly defending the somatic / germinal barrier using the value of non-maleficence (security). ”
For example, in August 2015, according to Evans, the American Society for Gene and Cell Therapy and the Japan Society of Gene Therapy issued a statement noting that “safety and ethical concerns” regarding the editing of the Human germ line are “serious enough to support a strong position against gene editing or gene modification in human cells to generate viable human zygotes with inherited germ line modifications.”
He concluded his arguments by calling on the molecular biology community to consider the speed at which advances in gene editing have come in recent years. âThe CRISPR revolution makes all kinds of interventions possible in the natural world, and these interventions have all their surrounding ethical debates.
âAs genetic tools become more and more powerful, we need to focus on why we use the tools – on our values ââ- or risk slipping into ‘what can be done has to be done’. ”
New gene editing tools reignite debate on germline alteration
John H. Evans. Set ethical limits on the editing of human genes after the fall of the somatic / germinal barrier, Proceedings of the National Academy of Sciences (2021). doi.org/10.1073/pnas.2004837117
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