Review | With CRISPR, humans can create their own evolutionary future

The indifferent process of Darwinian evolution by natural selection took a laborious 3.85 billion years to craft us from our unicellular microorganism precursors into the way we are today. En route there were many failures, including multiple extinct species of humans, whose fragmented skulls glare at us from vanished worlds.

Noting natural selection’s often baroque and paradoxical process, and its propensity to generate disease and impair longevity, the evolutionary biologist George C. Williams likened its craftsmanship of the human genome to the work of a “prankster.” If evolution were a college senior, it would probably graduate with a C average rather than cum laude.

We cannot rewind the tape of life to see how we might have been and whether humans are inevitable products of evolutionary processes, but as Kevin Davies states in his lively and enthralling “Editing Humanity,” our unprecedented ability to engineer genomes rapidly and efficiently offers humankind the possibility of contemplating what we might become. It provides us with the capabilities to actualize a synthetic evolutionary future. And it may allow the woolly mammoth and the dodo to be resurrected from the oblivion of extinction and facilitate the modification of all earthly creatures.

Given that humans originated from unicellular organisms, it is somewhat ironic that a simple molecular machine known as CRISPR, which was purloined from these microscopic beasts and which evolved to defend them from marauding viruses, forms the basis of the biological scalpel capable of implementing the most substantial alterations ever to be introduced into human genomes.

CRISPR, an acronym for “clustered regularly interspaced short palindromic repeats,” was not, Davies informs us, the first genome-editing tool. The Nobel Prize-winning molecular biologist Aaron Klug, working in Cambridge, England, in the 1980s, discovered a class of regulatory molecules known as zinc finger proteins in the egg of an African clawed toad. He realized that these DNA-binding proteins could be engineered to allow precise edits to be introduced into genomes. But while it was adept at doing this, the use of zinc finger protein editors required substantial resources and expertise.

The CRISPR breakthrough issued from its simplicity, which enabled it to become the Model T Ford of genome editing. Remarkably cheap and easy to use, this everyman technology swept across the world and enabled the democratization of genome editing.

Benefiting from his presence at some of the key moments in gene-editing history, and armed with humor and an enthusiastic writing style, Davies provides a compelling account of CRISPR’s discovery and the shenanigans accompanying its meteoric ascendance. These include the formation of biotechs, patent disputes, fallouts and disagreements over the limits of responsible editing.

All this culminated in the untimely and unethical use of CRISPR by the scientist He Jiankui to edit the germline DNA of human embryos, an irresponsible and cavalier act that affected the heredity of two girls forever. Davies’s account of this sobering episode in CRISPR’s short and turbulent history reminds us of the inherent dangers of genome editing and of the ease with which technologies may be subverted for totalitarian ends. Fortunately, many essential human characteristics, including free will, do not reduce to individual genes.

As is often the case with pivotal scientific discoveries, CRISPR originated as a result of curiosity-driven research, a fascination with nature’s wonders and an obsessive desire to comprehend them. The Spanish microbiologist Francisco Mojica, transfixed by an obscure bacterial species called Haloferax and its improbable survival in the high-salt conditions of the flats in the port city of Alicante, stumbled upon repetitive sequences in its DNA while searching for the genomic basis of its survival.

This observation would eventually reveal that CRISPR was a primitive bacterial immune system. After ripping pieces of DNA out of viral invaders, CRISPR displays them between the repetitive sequences to form a library of viral suspects. The viral fingerprints in this internal CRISPR library can then be weaponized, making small pieces of RNA that function as molecular GPS devices to guide a protein called Cas9 to the genome of an invading virus, which it snips in two.

The realization that CRISPR could be programmed to target any piece of DNA allowed it to be transformed into a genome-editing platform with limitless utility. Davies shows how the development of CRISPR resulted from the contributions of many individuals. In the search for heroes, the cooperative and synergistic nature of scientific discovery is often forgotten.

That we live in the age of genomic medicine cannot be doubted. The full impact of genome editing on human health can hardly be imagined. Its use to reprogram cells to cure cancer is but one of many examples of how it will touch our lives. The ultimate edit is of course a rewrite, and the impending completion of the synthetic genome of a yeast, by an international consortium led by New York University’s Jef Boeke, promises to usher in an age when complex genomes can be written from scratch.

Perhaps the crowning glory of any species is the moment when it learns to reinvent itself. But if this unfathomable power is not exercised with the greatest caution, it risks precipitating the moment when our humanity is irreversibly undermined.

Editing Humanity

The CRISPR Revolution and the New Era of Genome Editing

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