Introduction to the Special Issue on CRISPR George Q. Daley As i was finalizing this introduction to the Special Issue on CRISPR genome editing for Perspectives in Biology and Medicine, news broke that the Chinese scientist He Jiankui had been sentenced in Chinese court to three years in prison for "illegal medical practice" for his role in the creation of the world's first genome-edited babies. This official reprimand reinforced the worldwide condemnation and censure that followed He's announcement in November 2018 that his team at the Southern University of Science and Technology in Shenzhen, China, had used the CRISPR-Cas9 genome-editing tools on human embryos created via in vitro fertilization. He produced and brought to term two babies (and later a third) carrying mutations in the CCR5 gene, a critical co-receptor for HIV, in hopes of rendering these babies immune to infection with the virus that causes AIDS. The work was criticized as premature practice of an unproven and controversial biomedical technology, and vilified for its flouting of widely promulgated international guidelines. Numerous expert committees that had called for restraint, further research to understand the potential risks, and wider social dialogue to determine which, if any, of the many possible genetic changes that could be introduced into the human germline might one day be [End Page 1] deemed permissible. Scientists, bioethicists, and laypeople who had previously been at odds over whether genome editing of human embryos for the purpose of altering an individual's entire genetic constitution—and by virtue of passage through the reproductive germline, that of all of their offspring—should ever be practiced, were virtually united that the world's first experiment in human germline genome editing had been a gross violation of medical and bioethical norms. While the imprisonment of the first practitioner of human germline genome editing will likely dampen enthusiasm that might have been building in some quarters, an IVF clinic in Russia has boldly announced their intentions to create genome-edited babies, and application of this technology, however premature, may be inevitable. This volume is an important exercise in the critical dialogue that is essential if the potential application of this technology is ever to be managed for maximal benefit and minimal harm. Gene editing is not a new technology, nor is the genome editing of humans a novel concept barely entertained prior to the discovery of the CRISPR-Cas9 genome-editing toolkit. For more than a century and a half, dating from the time of Mendel's discovery of the rules of heredity, the later definition of the gene as units responsible for the generational passage of hereditary traits, and ultimately the discovery of DNA as the molecular vehicle of such inheritance, farmers and scientists have been engaged—wittingly, or unwittingly—in the manipulation of genetic traits through selective breeding or experimental interventions. The potential that scientists might one day prove capable of altering and defining human traits either chemically or genetically in the context of in vitro fertilization and embryo manipulation has long been the subject of critical commentary and fiction. Perhaps most notable was the publication in 1932 by Aldous Huxley of Brave New World, a dystopian view of a future society in which highly mechanized in vitro embryo manipulation produced babies preordained into specific castes of social strata. The modern era of gene editing began, arguably, in the Stanford laboratory of Paul Berg, who in 1972 published the creation of the world's first hybrid DNA molecule, a link between genes of the monkey tumor virus SV40 and a virus that infects bacteria, called lambda phage (Jackson, Symons, and Berg 1972). A natural next step was injecting this novel gene construct into the bacterial host Escherichia coli, a denizen of the human intestine. But Berg deferred this experiment because of concerns about the potential risks of propagating a monkey tumor virus within the human gut, and together with other scientists, he advocated for restrictions on certain types of recombinant DNA research (such as inserting toxins, antibiotic resistance, or cancer genes into bacteria) until safety concerns could be better addressed. Berg and colleagues organized a conference of scientists to address ways to ensure the...
Read full abstract