Early this year at the 2016 annual meeting of the American Association for the Advancement of Science, your blogger joined a huge, attentive, jam-packed crowd that was listening for the latest information on something called CRISPR, pronounced “crisper.” Their big reason for being there was to learn more about a technology that may change human life forever. For many of the meeting’s attendees this lecture was without doubt the pièce de resistance, the reason to be in Washington, D.C., on a very cold winter’s day.
Quiet reigned in the auditorium as we listened to the woman who discovered how to change the central control room of what we are, the genome, in a remarkably efficient way. She is Jennifer Doudna, and from the back rows she looked like a blonde coed. Of couse she was nothing of the sort. She is on the top rank of the world’s star biologists, and she runs her own world-class genetics laboratory at the University of California, Berkeley. Her specialty, CRISPR, is magic revealed. It is a thing of hope, controversy and incipient fear.
Ways of new ways of working with DNA have spurred biological discovery ever since Watson and Crick discovered the double helix. Making changes in the sets of genes that make up a genome, however, has been a tough problem that only nature has managed to solve. Even after scientists made inroads into the task of how nature recognizes specific DNA sequences, using nuclease enzymes, there was no immediate breakthrough.
Now that problem has been consigned to history. CRISPR is a vastly powerful new genetic engineering tool that has zoomed into the scientific spotlight with spectacular speed. It has re-engineered test-tube tissue and sterilized mosquito populations. Chinese scientists have experimented with nonviable human embryos and even adjusted the metabolic and immune systems of one of our primate relatives, cynomolgus monkeys.
Before the monkey announcement at the beginning of 2014, Doudna was more or less glued to her experimental work, teasing out the secrets of acquired immunity. When not at the laboratory she chose a quiet life – family life, country walks, that sort of thing. But she became haunted by a new concern. Monkeys are primates, people are primates. What happens in monkeys surely can happen in humans as well. Could genetic engineering change human lives? If so, for better or for worse? Would genetic engineering change human lives, or could the world be convinced to ensure that science stops short of, say, seeking physical “perfection” in its children? Doudna realized that scientists would have to explain the benefits and drawbacks of genetic engineering now that CRISPR was on a roll: they would have to temper their zeal for scientific discovery with their desire to ensure that the human organism would be tamper-proof except for the prevention of disease.
Jennifer Doudna changed her life and went on the lecture circuit in 2015. That year she and her research partner, Emmanuelle Charpentier, were listed among TIME magazine’s “100 most influential People.”
A lot of people are scared by CRISPR’s meteoric rise to scientific fame, some are delighted because the technique could wipe dread diseases from the human map, most of us are caught in between. The scientific community too is trapped amidships, captivated by CRISPR and at the same time desperate to do something to keep the technology from being misused. Yes, CRISPR will probably be able to ensure that you have a blue-eyed baby even if you and your spouse are brown-eyed. But nobody wants a planet dominated by a genetically engineered master race.
Eons ago CRISPR was invented by Mother Nature as a way of immunizing her flock from rogue genes transplanted in them to provide a foothold for predators and parasites. Among vast numbers of others, relatives of the famous staph infections were doubtless numbered among that flock, equipped with “gene drives” that could find harmful genes and replace them with copies of the helpful original ones. The first hint of great discovery occurred in 2007, when a yogurt company learned that the bacteria in its product had a mysterious ability to defend itself against viruses. The mystery was eventually solved with the discovery of CRISPR, an acronym for clustered regularly-interspaced short palindrome repeats, which describes how genes are arranged, as peculiar, repetitive bacterial DNA sequences, in the errant chromosome.
By 2015 natural CRISPR gene drives were found in yeast, fruit flies, and mosquitoes, and it was learned that in all cases the changes they made were passed on to offspring, generation after generation. With time the entire species would undergo a genomic rewiring job. In December of that year, wary of the deep ethical implications of CRISPR, scientists of major world academies called for suspension of research into making inheritable changes in the human genome. Two months later, British scientists won permission to alter human embryos with CRISPR or similar methods, with the agreement of an ethics board and with the proviso that these embryos had no prospect of becoming viable. CRISPR kits “for easy genome engineering” became available online.
Meantime, on December 21, 2015, German chemicals giant Bayer and CRISPR Therapeutics, co-founded by one of CRISPR’s pioneer scientists, Emmanuelle Charpentier. announced a joint venture designed specifically to “discover, develop and commercialize new breakthrough therapeutics to cure blood disorders, blindness, and congenital heart disease.”
Other linkups followed, including an AstraZeneca program that links the firm with Wellcome Trust Sanger, the Broad Institute, the Innovative Genomics Initiative, and Thermo Scientific Media. An AstraZeneca news release headlined plans “to use CRISPR technology for genome editing across its drug discovery platform.”
Bayer’s CRISPR news release explained that an enzyme named Cas9 acts as “molecular scissors” that can “cut and edit, or correct, disease-associated DNA in a cell.” Guided to the target gene sequence with ultimate precision by an RNA snippet, the “scissors” make a cut in the DNA, making it possible to replace the original sequence with an altered version.
The fast pace of CRISPR development is due to rapid progress in theory and research by Jennifer Doudna, Emmanuelle Charpentier, and their team at the University of California, Berkeley, and separate work by Feng Zhang and colleagues at the Broad Institute of Harvard and Massachusetts Institute of Technology. Claims to patent rights for the technology are now being adjudicated.
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This blog post is condensed from a magazine-length article that is currently looking for a home on the printed page.