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f there was one misstep that doomed the long and bitter fight by the University of California to wrest key CRISPR patents from the Broad Institute, it was star UC Berkeley scientistJennifer Doudnas habit of being scientifically cautious, realistic, and averse to overpromising.

A biochemist who co-led a breakthrough 2012 study of CRISPR-Cas9, Doudna repeatedly emphasized in interviews the challenges of repurposing the molecular system, which bacteria use to fend off viruses, to edit human genomes. The U.S. patent office, in a February rulingthat let the Broad keep its CRISPR patents (for now), relied heavily on those statements We werent sure if CRISPR/Cas9 would work in animal cells, for example to conclude that when scientists at the Broad CRISPRd human cells in 2013, it was a non-obvious advance and therefore deserving of patents.

So its striking that the careful, measured Doudna who said CRISPRing human cells and thereby curing devastating diseases would be a challenge is hardly in evidence in A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution, the new book she co-authored with her former student Samuel Sternberg. It goes on sale Tuesday.

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This Doudna doesnt hold back. We are on the cusp of a new age in genetic engineering and biological mastery, she and Sternberg write, dangling the prospect of life-changing treatments and lifesaving cures. She says she is not kidding that CRISPR could bring about woolly mammoths, winged lizards, and unicorns. It wont be long before CRISPR allows us to bend nature to our will.

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The hyperbole contrasts with CRISPRs stumbles, including altering parts of genomes (in lab studies, not patients yet) it wasnt supposed to. I dont think well have a version of CRISPR thats 100 percent perfect, so it comes down to a risk-benefit analysis, Sternberg, a biochemist at Caribou Biosciences (which Doudna co-founded), said in an interview. There has been phenomenal progress in understanding off-target effects; I think its a solvable problem. We have every reason to be optimistic but I hope we avoided overhyping and didnt give the impression that there would be windfall of cures in the next couple of years.

This is not a tell-all. The farthest Doudna goes in addressing the patent fight a disheartening twist is to say that because of such rivalries she experienced the gamut of human relationships, from deep friendships to disturbing betrayals. She doesnt name the betrayers.

An early reviewchastised Doudna for presenting herself as so flawless the book seems more concealing than revealing, not insightful [and] candid.

So what she does choose to reveal is fascinating, especially about her collaboration with Emmanuelle Charpentier. The two are so closely linked that all the prizes theyve won for CRISPR, theyve won together; among CRISPR watchers DoudnaandCharpentier is virtually a macro.

But the books account of their breakthrough experiment showing that CRISPR could be programmed to edit a precise spot in a genomeleaves a different impression. We read that Martin [Jinek, Doudnas postdoctoral fellow] showed and Martin labored tirelessly, Martin and I brainstormed and designed an experiment, and when Martin walked me through the data, Doudnaknew wed done it.

That work was described in the 2012 paper, which is widely recognized by prize committees, the European Patent Office, and many scientists as the Bastille moment for the CRISPR revolution. It identified the three crucial molecules in the CRISPR system one to cut, one to guide the cutting enzyme to its target DNA, one to activate the cutting enzyme that produced a programmable DNA-cutting machine. We had built the means to rewrite the code of life, Doudnaand Sternberg write. Nothing after that would ever be the same.

Although Doudna and her collaborators didnt actually change genomes in cells their CRISPR molecules altered cell-free DNA in test tubes that was an obvious next step. How difficult a next step was the core dispute in the patent fight and one that she repeatedly cautioned was no slam dunk. But Crack in Creation says that doing so was immediately clear to us, and there were good reasons to expect success.

That contrasts with her cautious statements, cited by the patent office, at the time. When Feng Zhang of the Broad Institute and George Church of Harvard used CRISPR to edit genes, it was just as we had proposed in 2012, according to the book. She waselated that her 2012 work inspired others to pursue a line of experimentation similar to our own.

Doudna became a public scientist shes given aTED talkand will appear on Sunday Night with Megyn Kelly because of her research, but also because she was instrumental in getting the scientific community to focus on ethical issues it raises, especially about editing embryos in a way that would be inherited by future generations (germline editing). She writes that she had nightmares that a man asking her about this was Hitler and that she began to feel a bit like Dr. Frankenstein.

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Her own moral journey is intriguing. She feels germline editing can be safe, and the its unnatural! argument doesnt carry much weight with me anymore, she writes. It seems to me that wed be justified in using CRISPR to eliminate genes that cause untold suffering, such as those for Huntingtons disease. When I think about the pain that genetic diseases cause families, the stakes are simply too high to exclude the possibility of eventually using germline editing, as an expert panel also concluded.

Doudnaacknowledges, however, that its difficult to see how wed do it equitably, especially when the line between therapy and enhancement is paper thin: Some families might purchase a genetic legacy that gives them less need for sleep, greater endurance, extra-strong bones, leaner or larger muscles, lower risk of diabetes and Alzheimers, even less armpit odor while other families muddle through with the genes nature gave them.

That threatens to transcribe our societies financial inequality into our genetic code, Doudna writes.

Her solution? Redoubl[ing] our commitment to building a society in which all humans are respected and treated equally, regardless of their genetic makeup.

Sharon Begley can be reached at sharon.begley@statnews.com Follow Sharon on Twitter @sxbegle

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CRISPR pioneer Doudna envisions a world of woolly mammoths and unicorns - STAT

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