'CRISPR' wows a world that also balks at the idea of gene-edited babies

CRISPR-Cas9 cover of Nature magazine, highlighted
therapeutic uses of gene editing

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 main reason for being in Washington, D.C., on a very cold winter’s day.

Quiet reigned in the auditorium as we listened to the woman who had discovered how to change the central control room of what we are, the genome, in a remarkably efficient way. The woman was Jennifer Doudna, and from the back rows she looked like a blond coed. Of course she is nothing of the sort. She is one 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. The acronym stands for clustered regularly-interspaced short palindrome repeats, which describes how certain genes are arranged, as peculiar, repetitive DNA sequences,in the the chromosomes of all eukaryotic forms of life, from humans to pine trees, octopi, and slime molds. Its secret lies in the fact that it can produce the gift of immunity against harmful or otherwise undesirable genetic characteristics.

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 some 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 genetic master race.

Eons ago CRISPR was invented by Mother Nature as a way of immunizing her flock from rogue genes transplanted in them as footholds for predators and parasites, equipping her flock with “gene drives” that could find harmful genes and replace them with copies of the helpful original ones. The CRISPR pattern of gene sequences was noted in 1987 by scientists at Osaka University, Japan, in the gut microbe e. coli. In 1972 Ruud Jansen and colleagues at Utrecht University, Netherlands, announced their discovery that that another set of genes would accompany CRISPR genes, and then rather naturally dubbed them CRISPR-associated (Cas) sequences. Another significant discovery occurred in 2007, when the Danish yogurt company Danisco (now owned by DuPont) learned that the bacteria in its product had a mysterious ability to defend against viruses. This natural antiviral agent turned out to be CRISPR.

By 2015 natural CRISPR gene drives had been identified in a number of organisms, including 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. Now it seems evident that natural CRISPR/Cas9 is at work in the chromosomes of all eukaryotic forms of life, from humans to whales, pine trees, octopi, and slime molds.

 In December of 2015, 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. Unfortunately, national codes differ, so research labs and gene-editing entrepreneurs have few ethical toolkits that are enforceable. Meanwhile, CRISPR kits “for easy genome engineering” are readily available online.

Meantime, on December 21, 2015, German chemicals giant Bayer and CRISPR Therapeutics, co-founded by one of CRISPR’s pioneer scientists, 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 big Swiss firm with Wellcome Trust Sanger, the Broad Institute, the Innovative Genomics Initiative, and Thermo Scientific Media.

The fast pace of CRISPR development is largely 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.