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Ethics of genome editing: Avoiding false equivalencies

Photo Courtesy of Wikimedia Commons
Photo Courtesy of Wikimedia Commons

Centuries from now, history will likely associate 2018 with the birth of the first genome-edited babies. This event, disclosed in November by Dr. He Jiankui from China, dragged humanity further into a murky ethical quagmire surrounding human embryonic germline editing. I stand with the vast majority of my colleagues in the scientific community who believe that that the experiment revealed in November was ethically inappropriate, lacked medical merit and failed to conform to international norms. However, despite this deeply flawed example of human germline experimentation, increasing investments and research can benefit our society. Proper use of genome editing can feed millions, treat cancer and alleviate suffering. 

Genome editing refers to mixing, adding and/or subtracting building blocks of DNA—those As, Gs, Cs, and Ts that act as a code of every living organism on our planet. Changes in our DNA genotype can lead to changes in our phenotype, the set of characteristics which include everything from our eye color to proteins that can increase or reduce risk of acquiring an infection or cancer. To some, genome editing offers possibility of ridding humanity of devastating heritable diseases. To others, it is a chance for the rich and privileged to provide their children with even more advantages. 

Debate on the ethics and utility of genome editing often overlooks two important considerations. The first consideration is to what kind of system genome editing is applied. To most, experimentation in plants and mice are ethically disparate from experimentation in humans. 

The second consideration is the type of cell being edited. Like consideration of the system, a similar ethical dichotomy exists when genome editing technology is applied to somatic cells (i.e., cells in the body for which changes cannot be passed to future generations) versus germline cells (i.e., eggs, sperm, or an early embryonic stage that results in editing all or most cells in a human; therefore edits will enter our population with a potential to be passed to future generations). Somatic cell genetic engineering has occurred safely for over two decades, and is closely regulated. For example, ongoing clinical trials to treat disorders of red blood cells, such as sickle cell disease, use CRISPR/Cas9 to edit hemoglobin genes in red blood cell precursors, which are then infused into patients.  Any changes, or mistakes, that occur during this somatic cell editing process are limited to the individual.  When engaging in discourse regarding genome editing technology, placing all systems and cell types into the same ethical basket is analogous to falsely equating different types of nuclear technology: while the merits of such powerful technology warrant thoughtful debate and thorough scrutiny, there is a clear ethical distinction between using atomic energy to power a city or to bomb it.

Applying genome editing technology to crops has, and will continue to, save lives. Further investment in this technology could help close gaps in global inequality. Nobel laureate Sir Richard Roberts estimates that failure to utilize genome editing technology in plants to provide vitamin supplementation has resulted in the deaths of millions in resource-poor countries. Potential misuse of most any technology could have harmful effects on society, and genome editing technologies for improving crop yields and health benefits are no different. However, the degree of misinformation disseminated about genetically modified organisms (GMOs) seems higher relative to other technologies. Scare tactics, such as that genetically modified plants will somehow cross DNA over into humans, are not infrequently repeated. All plants we eat contain DNA, modified or otherwise. The four DNA nucleotides do not change with genome editing. All that changes is the amount of, or relative ratio of, these nucleotides. We digest the genomes from plant GMO or ‘non GMO’ DNA equivalently. Eating a plant from either a modified variant or a normal variant conveys no risk of either acquiring, or passing on to our children, the ability to photosynthesize. Suggestions that we could acquire other traits or become mutants ourselves from eating genetically modified organisms are not founded in science. 

While genome editing technology can provide our planet with more nutrients to help children grow up healthy, it can also help us as we age. For example, genome editing of human somatic cells offers the opportunity to reprogram our immune cells to fight cancer. In recently FDA approved CAR T-cell therapy, a patient’s own immune cells can be isolated, efficiently and specifically genetically edited with technology (such as CRISPR/Cas9) to target certain types of cancer, and reintroduced back into her or his body. While this technology is currently resource-intensive and expensive, the promise of using this technology to save our loved ones is very real. However, without further research and clinical trials utilizing this genome somatic cell editing, CAR T-cell therapy will only target a small subset of cancers and neither be widely accessible nor affordable. 

Similarly, using genome editing technology within non-germline cells (such as those grown in petri-like dishes within incubators) for laboratory research will allow us to discover new drug targets, as well as provide us with a deeper understanding of how our biological world functions. Initial studies using recombinant DNA in bacterial cells in the 1970s, and later mammalian cells, led to the ability to synthesize insulin, which revolutionized treatment for those with diabetes. In addition, genome editing can be used to quickly and efficiency knock in or knock out certain proteins in these cells to see if they might have relevance in cancer or inflammation. Genome editing of non-germline human cells in the laboratory has occurred for decades and is responsibly regulated. Introducing legislative restrictions on genome editing without consideration for either the system or the cell type would be profoundly detrimental to scientific discovery. 

Less than a century since Franklin, Watson and Crick conducted foundational experiments defining the structure of DNA, the first genome-edited human babies have been brought to term. As our society continues to grapple with ethical implications, let us be wary of sweeping generalities and false equivalencies that could undermine responsibly using genome editing technology to create a more healthy and prosperous world for all of us. 

Jeffrey S. Smith is a 7th year M.D./Ph.D. student. He utilized genome editing technology during his thesis work with Dr. Sudarshan Rajagopal and Nobel laureate Dr. Robert J. Lefkowitz. Jeffrey discussed the ethical implications of genome editing as representative of the United States with Dr. Richard Roberts and others Nobel laureates at the 68th Lindau Laureate meeting in June of 2018. You can follow him on twitter @jeffsmith1342

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