Global Health and Social Medicine, Harvard University, 641 Huntington Avenue, Boston, MA 02115. Email: neal_baer@hms.harvard.edu. Perspectives in Biology and Medicine, volume 63, number 1 (winter 2020): 14–27.© 2020 by Johns Hopkins University Press 14 Commentary code dread? Neal Baer CRISPR keeps me up at night. I marvel at its potential to cure insidious genetic diseases and scourges like malaria. I shudder at the ways it might be misused to create biological weapons. What frightens me most, though, is what I can’t predict: how will we use CRISPR? How will it change evolution? How will it redefine the very nature of our existence? CRISPR (clustered regularly interspaced short palindromic repeats) is an ingenious cut-and-paste system that homes in on a particular DNA gene sequence and then, using Cas9 enzymes, snips it out. That sequence is then replaced with a new one that rewrites or repairs the original. Two different cells—somatic, from the body, and germline, from gametes—can be manipulated using CRISPR. Yet only germline genome cells can be inherited by future offspring. In 2019, scientists in the US used this method to treat a patient with sickle cell disease. In Europe, scientists treated one with beta thalassemia. Both patients, suffering from genetic mutations of their hemoglobin genes, underwent bone marrow ablation. Then CRISPR was used to modify their own blood-producing stem cells to make healthy fetal hemoglobin. The CRISPR cells were engrafted in each patient—known as a somatic treatment—without the usual worry of donor rejection. Both patients are reported to be doing well, making healthy fetal Commentary 15 winter 2020 • volume 63, number 1 hemoglobin. These CRISPR-based treatments have kept them from needing transfusions or hospitalization for severe anemia or vaso-occlusive crises. Using CRISPR to treat genetic mutations like these, which cause inordinate suffering and a shortened life span, is nothing short of miraculous. Why worry, then, about using CRISPR as long as it can be made safe in the clinical setting? Repairing the somatic genetic mutations in an individual means that scientists can do the same to the germline genome, and this could change human evolution. “That raises the possibility, more realistically than ever before,” notes Michael Specter (2015), a well-known science journalist, “that scientists will be able to rewrite the fundamental code of life, with consequences for future generations that we may never anticipate” (54). One method for accomplishing such a profound feat of editing is by using a CRISPR-based gene-drive system that preferentially propagates a genetic trait through an organism and its offspring. Imagine using CRISPR to make a female mosquito infertile, causing it to be incapable of laying eggs. Instead of a 50% chance that the disruptive gene is inherited , a CRISPR gene copies itself, making the inheritance 100%, leading to a self-destructing mosquito. How do we conceive of any unintended consequences that could come from using CRISPR gene drives to make female mosquitoes infertile in order to eradicate malaria? Can we ever be certain of the environmental impact of such an undertaking , even if it means preventing a thousand children from dying of malaria each day? Can we prevent the malevolent use of CRISPR to conjure up bacteria or viruses that can wipe out millions or destroy food crops the world depends on? “If you can edit a creature to solve a problem,” declares gene-drive discoverer Kevin Esvelt (2019), “you can edit a creature to create a problem.” CRISPR has vaulted us into a binary world of hope and potential devastation. It can provide us with cures that will alleviate suffering, along with terrifying bioweapons that could destroy us; treatments for diseases that assail humankind, and enhancements that could give the wealthy an even greater societal edge—what the political theorist Michael Sandel (2004) warns could lead to two subspecies, “the enhanced and the merely natural.” This dual-use research of concern “could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security” (NIH 2019). CRISPR is not the first exterminating peril the world has faced. Scientists and...
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Jun 1, 2020
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