A Crack in Creation: Gene Editing and the Unthinkable Power to Control EvolutionA Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution
As Human Gene-Editing Advances, Doudna Says Ethical Discussions Can't Wait
CRISPR Pioneer Doudna: Humans on Cusp of 'New Age in Biological Mastery'
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"caption": "Products and therapies using CRISPR gene editing are inching closer to us every day. Now is the time, scientists say, for the public to draw ethical lines. ",
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"slug": "as-human-gene-editing-advances-doudna-says-ethical-discussions-cant-wait",
"title": "As Human Gene-Editing Advances, Doudna Says Ethical Discussions Can't Wait",
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"content": "\u003cp>If you want to have a role in shaping the near and coming future of biotechnology, the time is now. A science degree is not required, but a sense of urgency is.\u003c/p>\n\u003cp>This was the primary takeaway from Jennifer Doudna’s recent public remarks at\u003ca href=\"http://crisprcon.org/\" target=\"_blank\" rel=\"noopener noreferrer\"> CRISPRcon\u003c/a>, a two day event at UC Berkeley, intended to get nonspecialists talking about the promise and potential peril of the fast-moving biotech landscape.\u003c/p>\n\u003cp>“Decisions about gene editing have an impact on all of us,” said Michael Krasney, host of KQED’s “Forum” radio program and the CRISPRcon emcee. “That’s why there are no outsiders in discussing this topic.” (For a primer on how CRISPR gene editing works, check out our story “\u003ca href=\"https://ww2.kqed.org/futureofyou/2015/12/30/a-crispr-solution-to-bubble-boy-disease/\" target=\"_blank\" rel=\"noopener noreferrer\">CRISPR: What You Need to Know About the Medical Science ‘Breakthrough of the Year\u003c/a>.”)\u003c/p>\n\u003caside class=\"pullquote alignright\">“We can no longer say, well there’s a lot of technology development to be done before we have to worry about that application, it’s now a question of ‘We know this can work, are we willing to go there or not?'” \u003ccite>Jennifer Doudna, one of the inventors of CRISPR/Cas9 gene-editing technology\u003c/cite>\u003c/aside>\n\u003cp>The National Academies of Sciences, Engineering and Medicine wants public input, as well. The rationale is, if it affects the public, the public should have a say.\u003c/p>\n\u003cp>\u003cstrong>What’s at Stake\u003c/strong>\u003c/p>\n\u003cp>[ad fullwidth]\u003c/p>\n\u003cp>In her new book, “\u003ca href=\"http://www.acrackincreation.com/\" target=\"_blank\" rel=\"noopener noreferrer\">A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution\u003c/a>,” Doudna (who co-authored the book with former student Samuel Sternberg) writes humans are “on the cusp of a new age in genetic engineering and biological mastery.”\u003c/p>\n\u003cp>“It won’t be long before CRISPR allows us to bend nature to our will.”\u003c/p>\n\u003cp>CRISPR applications could bring us \u003ca href=\"https://www.sciencedaily.com/releases/2017/05/170518140335.htm\" target=\"_blank\" rel=\"noopener noreferrer\">higher tomato yields\u003c/a> or cattle \u003ca href=\"https://geneticliteracyproject.org/2016/05/11/gene-edited-hornless-cow-improve-animal-welfare-regulatory-fate-unclear/\" target=\"_blank\" rel=\"noopener noreferrer\">born without horns\u003c/a> (allowing livestock to avoid the potentially painful procedure of having them removed). Ongoing medical research using CRISPR includes \u003ca href=\"https://www.nature.com/news/first-crispr-clinical-trial-gets-green-light-from-us-panel-1.20137\" target=\"_blank\" rel=\"noopener noreferrer\">gene editing to target immune response\u003c/a> in cancer patients and to \u003ca href=\"https://www.nature.com/news/crispr-deployed-to-combat-sickle-cell-anaemia-1.20782\" target=\"_blank\" rel=\"noopener noreferrer\">correct sickle-cell anemia\u003c/a>, a painful blood disorder.\u003c/p>\n\u003cp>But the $10 million question at CRISPRcon loomed large:\u003c/p>\n\u003cp>“How do you decide which genes are appropriate for germline editing?” asked a woman in the audience, during a question and answer session with Doudna. Germline editing means that the changes made affect sperm or egg cells, and therefore can be inherited.\u003c/p>\n\u003cp>[contextly_sidebar id=”HfCYio1aAJwJdg2Ip7LwMBF1sWeN5NFY”]”That’s a question that could be debated and discussed for the entire time of the conference,” said Doudna. But her short answer, referencing a \u003ca href=\"http://www.nationalacademies.org/gene-editing/consensus-study/index.htm\" target=\"_blank\" rel=\"noopener noreferrer\">recent report with recommendations\u003c/a> from the National Academies, was, “We look for situations where there would be no other reasonable way to deal with a genetic disease other than gene editing. And when you think about it that way, those situations are rather rare.”\u003c/p>\n\u003cp>Preimplantation genetic diagnosis (for parents using in vitro fertilization) and genetic counseling can offer routes to avoid serious genetic mutations without gene editing. This latter technique would, however, require parents to decide if they are willing to terminate a pregnancy.\u003c/p>\n\u003cp>Doudna believes that in most cases genetic counseling and preimplantation genetic diagnosis are sufficient to deal with disorders caused by a single gene. But some couples might not have any other option to conceive a healthy embryo outside of editing their genes. For example, if both parents both have the same disease-causing gene, “That’s an issue where gene editing could be relevant in the future.”\u003c/p>\n\u003cp>For any parents who want to select for green-eyed, athletic geniuses, their best bet is still a random roll of the dice, not gene-editing, if the National Academies has anything to do with it. “Do not proceed at this time with human genome editing for purposes other than treatment or prevention of disease and disability,” the study recommends.\u003c/p>\n\u003cp>But the question of whether embryos should be edited to avoid disease and disability has reached new urgency, says Doudna, with the publication several weeks ago of the first \u003ca href=\"https://ww2.kqed.org/futureofyou/2017/07/27/scientists-in-us-edit-human-embryos-with-crispr-for-first-time-reports-suggest/\" target=\"_blank\" rel=\"noopener noreferrer\">paper\u003c/a> that lays out a good protocol (a written procedure) for targeting a gene linked to disease. It has the potential of being useful in clinical applications.\u003c/p>\n\u003cp>“What they showed, importantly,” said Doudna, “was that there was very few off-target effects [unintended changes] and also they could avoid something called ‘mosaicism’. ” That arises when the desired edit occurs in only some of the cells in the developing embryo. Both edited and non-editing cells replicate, resulting in an organism with a genetic patchwork, which may or may not be harmful.\u003c/p>\n\u003cp>“We now understand that, when applied in certain ways this technology can be very robust, in viable human embryos. We can no longer say, ‘Well, there’s a lot of technology development to be done before we have to worry about that application.’ It’s now a question of, ‘We know this can work, are we willing to go there or not?’ ”\u003c/p>\n\u003cp>Since CRISPRcon, the paper in question has come in for some \u003ca href=\"https://ipscell.com/2017/08/doubts-raised-on-key-points-of-nature-paper-on-crispr-gene-editing-of-human-embryos/\" target=\"_blank\" rel=\"noopener noreferrer\">recent criticism from scientists\u003c/a> not involved in the research. They call into question the main conclusions of the paper and say more definitive studies are needed. That said, most scientists believe precise editing in embryos will be possible someday, and likely someday soon.\u003c/p>\n\u003cp>\u003c/p>\n\u003cp>For members of the public eager to be part of the debate, events like CRISPRcon provide a rare forum with scientists like Doudna who have \u003ca href=\"https://ipscell.com/2015/06/doudnacongress/\" target=\"_blank\" rel=\"noopener noreferrer\">testified before Congress\u003c/a> regarding the science and ethics of gene editing. But for the average person on the street, the most direct route to voicing opinions and concerns may be \u003ca href=\"http://www.nationalacademies.org/gene-editing/consensus-study/index.htm\" target=\"_blank\" rel=\"noopener noreferrer\">submitting comments\u003c/a> on the homepage of the National Academies’ Human Gene-Editing Initiative. Of course, there is also the tried and true method of \u003ca href=\"https://callyourrep.co/\" target=\"_blank\" rel=\"noopener noreferrer\">calling your representatives\u003c/a>.\u003c/p>\n\n",
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"content": "\u003cdiv class=\"post-body\">\u003cp>\u003cp>If you want to have a role in shaping the near and coming future of biotechnology, the time is now. A science degree is not required, but a sense of urgency is.\u003c/p>\n\u003cp>This was the primary takeaway from Jennifer Doudna’s recent public remarks at\u003ca href=\"http://crisprcon.org/\" target=\"_blank\" rel=\"noopener noreferrer\"> CRISPRcon\u003c/a>, a two day event at UC Berkeley, intended to get nonspecialists talking about the promise and potential peril of the fast-moving biotech landscape.\u003c/p>\n\u003cp>“Decisions about gene editing have an impact on all of us,” said Michael Krasney, host of KQED’s “Forum” radio program and the CRISPRcon emcee. “That’s why there are no outsiders in discussing this topic.” (For a primer on how CRISPR gene editing works, check out our story “\u003ca href=\"https://ww2.kqed.org/futureofyou/2015/12/30/a-crispr-solution-to-bubble-boy-disease/\" target=\"_blank\" rel=\"noopener noreferrer\">CRISPR: What You Need to Know About the Medical Science ‘Breakthrough of the Year\u003c/a>.”)\u003c/p>\n\u003caside class=\"pullquote alignright\">“We can no longer say, well there’s a lot of technology development to be done before we have to worry about that application, it’s now a question of ‘We know this can work, are we willing to go there or not?'” \u003ccite>Jennifer Doudna, one of the inventors of CRISPR/Cas9 gene-editing technology\u003c/cite>\u003c/aside>\n\u003cp>The National Academies of Sciences, Engineering and Medicine wants public input, as well. The rationale is, if it affects the public, the public should have a say.\u003c/p>\n\u003cp>\u003cstrong>What’s at Stake\u003c/strong>\u003c/p>\n\u003cp>\u003c/p>\u003c/div>",
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"content": "\u003cdiv class=\"post-body\">\u003cp>\u003c/p>\n\u003cp>In her new book, “\u003ca href=\"http://www.acrackincreation.com/\" target=\"_blank\" rel=\"noopener noreferrer\">A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution\u003c/a>,” Doudna (who co-authored the book with former student Samuel Sternberg) writes humans are “on the cusp of a new age in genetic engineering and biological mastery.”\u003c/p>\n\u003cp>“It won’t be long before CRISPR allows us to bend nature to our will.”\u003c/p>\n\u003cp>CRISPR applications could bring us \u003ca href=\"https://www.sciencedaily.com/releases/2017/05/170518140335.htm\" target=\"_blank\" rel=\"noopener noreferrer\">higher tomato yields\u003c/a> or cattle \u003ca href=\"https://geneticliteracyproject.org/2016/05/11/gene-edited-hornless-cow-improve-animal-welfare-regulatory-fate-unclear/\" target=\"_blank\" rel=\"noopener noreferrer\">born without horns\u003c/a> (allowing livestock to avoid the potentially painful procedure of having them removed). Ongoing medical research using CRISPR includes \u003ca href=\"https://www.nature.com/news/first-crispr-clinical-trial-gets-green-light-from-us-panel-1.20137\" target=\"_blank\" rel=\"noopener noreferrer\">gene editing to target immune response\u003c/a> in cancer patients and to \u003ca href=\"https://www.nature.com/news/crispr-deployed-to-combat-sickle-cell-anaemia-1.20782\" target=\"_blank\" rel=\"noopener noreferrer\">correct sickle-cell anemia\u003c/a>, a painful blood disorder.\u003c/p>\n\u003cp>But the $10 million question at CRISPRcon loomed large:\u003c/p>\n\u003cp>“How do you decide which genes are appropriate for germline editing?” asked a woman in the audience, during a question and answer session with Doudna. Germline editing means that the changes made affect sperm or egg cells, and therefore can be inherited.\u003c/p>\n\u003cp>\u003c/p>\u003cp>\u003c/p>\u003cp>”That’s a question that could be debated and discussed for the entire time of the conference,” said Doudna. But her short answer, referencing a \u003ca href=\"http://www.nationalacademies.org/gene-editing/consensus-study/index.htm\" target=\"_blank\" rel=\"noopener noreferrer\">recent report with recommendations\u003c/a> from the National Academies, was, “We look for situations where there would be no other reasonable way to deal with a genetic disease other than gene editing. And when you think about it that way, those situations are rather rare.”\u003c/p>\n\u003cp>Preimplantation genetic diagnosis (for parents using in vitro fertilization) and genetic counseling can offer routes to avoid serious genetic mutations without gene editing. This latter technique would, however, require parents to decide if they are willing to terminate a pregnancy.\u003c/p>\n\u003cp>Doudna believes that in most cases genetic counseling and preimplantation genetic diagnosis are sufficient to deal with disorders caused by a single gene. But some couples might not have any other option to conceive a healthy embryo outside of editing their genes. For example, if both parents both have the same disease-causing gene, “That’s an issue where gene editing could be relevant in the future.”\u003c/p>\n\u003cp>For any parents who want to select for green-eyed, athletic geniuses, their best bet is still a random roll of the dice, not gene-editing, if the National Academies has anything to do with it. “Do not proceed at this time with human genome editing for purposes other than treatment or prevention of disease and disability,” the study recommends.\u003c/p>\n\u003cp>But the question of whether embryos should be edited to avoid disease and disability has reached new urgency, says Doudna, with the publication several weeks ago of the first \u003ca href=\"https://ww2.kqed.org/futureofyou/2017/07/27/scientists-in-us-edit-human-embryos-with-crispr-for-first-time-reports-suggest/\" target=\"_blank\" rel=\"noopener noreferrer\">paper\u003c/a> that lays out a good protocol (a written procedure) for targeting a gene linked to disease. It has the potential of being useful in clinical applications.\u003c/p>\n\u003cp>“What they showed, importantly,” said Doudna, “was that there was very few off-target effects [unintended changes] and also they could avoid something called ‘mosaicism’. ” That arises when the desired edit occurs in only some of the cells in the developing embryo. Both edited and non-editing cells replicate, resulting in an organism with a genetic patchwork, which may or may not be harmful.\u003c/p>\n\u003cp>“We now understand that, when applied in certain ways this technology can be very robust, in viable human embryos. We can no longer say, ‘Well, there’s a lot of technology development to be done before we have to worry about that application.’ It’s now a question of, ‘We know this can work, are we willing to go there or not?’ ”\u003c/p>\n\u003cp>Since CRISPRcon, the paper in question has come in for some \u003ca href=\"https://ipscell.com/2017/08/doubts-raised-on-key-points-of-nature-paper-on-crispr-gene-editing-of-human-embryos/\" target=\"_blank\" rel=\"noopener noreferrer\">recent criticism from scientists\u003c/a> not involved in the research. They call into question the main conclusions of the paper and say more definitive studies are needed. That said, most scientists believe precise editing in embryos will be possible someday, and likely someday soon.\u003c/p>\n\u003cp>\u003c/p>\n\u003cp>For members of the public eager to be part of the debate, events like CRISPRcon provide a rare forum with scientists like Doudna who have \u003ca href=\"https://ipscell.com/2015/06/doudnacongress/\" target=\"_blank\" rel=\"noopener noreferrer\">testified before Congress\u003c/a> regarding the science and ethics of gene editing. But for the average person on the street, the most direct route to voicing opinions and concerns may be \u003ca href=\"http://www.nationalacademies.org/gene-editing/consensus-study/index.htm\" target=\"_blank\" rel=\"noopener noreferrer\">submitting comments\u003c/a> on the homepage of the National Academies’ Human Gene-Editing Initiative. Of course, there is also the tried and true method of \u003ca href=\"https://callyourrep.co/\" target=\"_blank\" rel=\"noopener noreferrer\">calling your representatives\u003c/a>.\u003c/p>\n\n\u003c/div>\u003c/p>",
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"content": "\u003cp>If there was one misstep that doomed the \u003ca href=\"https://www.statnews.com/2017/04/13/crispr-patent-uc-appeal/\">long and bitter fight\u003c/a> by the University of California to wrest key CRISPR patents from the Broad Institute, it was star UC Berkeley scientist Jennifer Doudna’s habit of being scientifically cautious, realistic, and averse to overpromising.\u003c/p>\n\u003cp>A biochemist who co-led a breakthrough \u003ca href=\"http://science.sciencemag.org/content/337/6096/816\" target=\"_blank\" rel=\"noopener noreferrer\">2012 study\u003c/a> 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 \u003ca href=\"https://www.statnews.com/2017/02/15/crispr-patent-ruling/\">ruling\u003c/a> that let the Broad keep its CRISPR patents (for now), relied heavily on those statements — “We weren’t sure if CRISPR/Cas9 would work in … animal cells,” for example — to conclude that when scientists at the Broad \u003ca href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795411/\" target=\"_blank\" rel=\"noopener noreferrer\">CRISPR’d human cells\u003c/a> in 2013, it was a non-obvious advance and therefore deserving of patents.\u003c/p>\n\u003cp class=\"danger-zone\">So it’s striking that the careful, measured Doudna who said CRISPR’ing 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 went on sale last week.\u003c/p>\n\u003cp class=\"danger-zone\">This Doudna doesn’t 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 won’t be long before CRISPR allows us to bend nature to our will.”\u003c/p>\n\u003cp class=\"danger-zone\">The hyperbole contrasts with CRISPR’s stumbles, including altering parts of genomes (in lab studies, not patients yet) it wasn’t supposed to. “I don’t think we’ll have a version of CRISPR that’s 100 percent perfect, so it comes down to a risk-benefit analysis,” Sternberg, a biochemist at \u003ca href=\"https://www.statnews.com/2016/06/22/rachel-haurwitz-crispr-caribou/\">Caribou Biosciences\u003c/a> (which Doudna co-founded), said in an interview. “There has been phenomenal progress in understanding off-target effects; I think it’s a solvable problem. … We have every reason to be optimistic but I hope we avoided overhyping and didn’t give the impression that there would be windfall of cures in the next couple of years.”\u003c/p>\n\u003cp>[ad fullwidth]\u003c/p>\n\u003cp>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 doesn’t name the betrayers.\u003c/p>\n\u003cp>An early \u003ca href=\"https://www.nature.com/nature/journal/v546/n7656/full/546030a.html\" target=\"_blank\" rel=\"noopener noreferrer\">review\u003c/a> chastised Doudna for presenting herself as “so flawless” the book “seems more concealing than revealing,” not “insightful [and] candid.”\u003c/p>\n\u003cp>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 they’ve won for CRISPR, they’ve won together; among CRISPR watchers “Doudna and Charpentier” is virtually a macro.\u003c/p>\n\u003cp>But the book’s account of their breakthrough experiment showing that CRISPR could be programmed to edit a precise spot in a genome leaves a different impression. We read that “Martin [Jinek, Doudna’s postdoctoral fellow] showed” and “Martin labored tirelessly,” “Martin and I brainstormed” and “designed an experiment,” and when “Martin walked me through the data,” Doudna knew “we’d done it.”\u003c/p>\n\u003cp>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,” Doudna and Sternberg write. “Nothing after that would ever be the same.”\u003c/p>\n\u003cp>Although Doudna and her collaborators didn’t 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.”\u003c/p>\n\u003cp>That contrasts with her cautious statements, cited by the patent office, at the time. When \u003ca href=\"https://www.statnews.com/2015/11/06/hollywood-inspired-scientist-rewrite-code-life/\">Feng Zhang\u003c/a> of the Broad Institute and \u003ca href=\"https://www.statnews.com/2017/06/08/george-church-narcolepsy/\">George Church\u003c/a> of Harvard used CRISPR to edit genes, it was “just as we had proposed in 2012,” according to the book. She was elated that her 2012 work “inspired others to pursue a line of experimentation similar to our own.”\u003c/p>\n\u003cp>Doudna became a public scientist — she’s given a \u003ca href=\"https://www.ted.com/talks/jennifer_doudna_we_can_now_edit_our_dna_but_let_s_do_it_wisely\" target=\"_blank\" rel=\"noopener noreferrer\">TED talk\u003c/a> and 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.”\u003c/p>\n\u003cp>Her own moral journey is intriguing. She feels germline editing can be safe, and the “it’s unnatural!” argument “doesn’t carry much weight with me anymore,” she writes. “It seems to me that we’d be justified in using” CRISPR to eliminate genes that cause untold suffering, such as those for Huntington’s 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 \u003ca href=\"https://www.statnews.com/2017/02/14/national-academy-crispr-report/\">concluded\u003c/a>.\u003c/p>\n\u003cp>Doudna acknowledges, however, that “it’s difficult to see how we’d 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 Alzheimer’s, even less armpit odor — while other families muddle through with the genes nature gave them.\u003c/p>\n\u003cp>That threatens to “transcribe our societies’ financial inequality into our genetic code,” Doudna writes.\u003c/p>\n\u003cp>Her solution? “Redoubl[ing] our commitment to building a society in which all humans are respected and treated equally, regardless of their genetic makeup.”\u003c/p>\n\u003cp>\u003cem>Update, June 14: Doudna, whose office cancelled an interview with STAT before this story ran, said in an email that “positioning Martin Jinek’s role to your readers as above the work of Emmanuelle Charpentier is incorrect and unfair. Our work was conducted closely with Emmanuelle, whose contributions and insights including the role of tracrRNA in the DNA targeting complex were a key aspect of the development of CRISPR-Cas as a gene editing technology.”\u003c/em>\u003c/p>\n\u003cp>\u003cem>\u003cspan style=\"font-weight: 400\">This \u003ca href=\"https://www.statnews.com/2017/06/11/crispr-jennifer-doudna-book/\" target=\"_blank\" rel=\"noopener noreferrer\">story \u003c/a>was originally published by STAT, an online publication of Boston Globe Media that covers health, medicine, and scientific discovery. \u003c/span>\u003c/em>\u003c/p>\n\u003cp> \u003c/p>\n\u003cp>[ad floatright]\u003c/p>\n\u003cp> \u003c/p>\n\n",
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"content": "\u003cdiv class=\"post-body\">\u003cp>\u003cp>If there was one misstep that doomed the \u003ca href=\"https://www.statnews.com/2017/04/13/crispr-patent-uc-appeal/\">long and bitter fight\u003c/a> by the University of California to wrest key CRISPR patents from the Broad Institute, it was star UC Berkeley scientist Jennifer Doudna’s habit of being scientifically cautious, realistic, and averse to overpromising.\u003c/p>\n\u003cp>A biochemist who co-led a breakthrough \u003ca href=\"http://science.sciencemag.org/content/337/6096/816\" target=\"_blank\" rel=\"noopener noreferrer\">2012 study\u003c/a> 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 \u003ca href=\"https://www.statnews.com/2017/02/15/crispr-patent-ruling/\">ruling\u003c/a> that let the Broad keep its CRISPR patents (for now), relied heavily on those statements — “We weren’t sure if CRISPR/Cas9 would work in … animal cells,” for example — to conclude that when scientists at the Broad \u003ca href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795411/\" target=\"_blank\" rel=\"noopener noreferrer\">CRISPR’d human cells\u003c/a> in 2013, it was a non-obvious advance and therefore deserving of patents.\u003c/p>\n\u003cp class=\"danger-zone\">So it’s striking that the careful, measured Doudna who said CRISPR’ing 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 went on sale last week.\u003c/p>\n\u003cp class=\"danger-zone\">This Doudna doesn’t 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 won’t be long before CRISPR allows us to bend nature to our will.”\u003c/p>\n\u003cp class=\"danger-zone\">The hyperbole contrasts with CRISPR’s stumbles, including altering parts of genomes (in lab studies, not patients yet) it wasn’t supposed to. “I don’t think we’ll have a version of CRISPR that’s 100 percent perfect, so it comes down to a risk-benefit analysis,” Sternberg, a biochemist at \u003ca href=\"https://www.statnews.com/2016/06/22/rachel-haurwitz-crispr-caribou/\">Caribou Biosciences\u003c/a> (which Doudna co-founded), said in an interview. “There has been phenomenal progress in understanding off-target effects; I think it’s a solvable problem. … We have every reason to be optimistic but I hope we avoided overhyping and didn’t give the impression that there would be windfall of cures in the next couple of years.”\u003c/p>\n\u003cp>\u003c/p>\u003c/div>",
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"content": "\u003cdiv class=\"post-body\">\u003cp>\u003c/p>\n\u003cp>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 doesn’t name the betrayers.\u003c/p>\n\u003cp>An early \u003ca href=\"https://www.nature.com/nature/journal/v546/n7656/full/546030a.html\" target=\"_blank\" rel=\"noopener noreferrer\">review\u003c/a> chastised Doudna for presenting herself as “so flawless” the book “seems more concealing than revealing,” not “insightful [and] candid.”\u003c/p>\n\u003cp>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 they’ve won for CRISPR, they’ve won together; among CRISPR watchers “Doudna and Charpentier” is virtually a macro.\u003c/p>\n\u003cp>But the book’s account of their breakthrough experiment showing that CRISPR could be programmed to edit a precise spot in a genome leaves a different impression. We read that “Martin [Jinek, Doudna’s postdoctoral fellow] showed” and “Martin labored tirelessly,” “Martin and I brainstormed” and “designed an experiment,” and when “Martin walked me through the data,” Doudna knew “we’d done it.”\u003c/p>\n\u003cp>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,” Doudna and Sternberg write. “Nothing after that would ever be the same.”\u003c/p>\n\u003cp>Although Doudna and her collaborators didn’t 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.”\u003c/p>\n\u003cp>That contrasts with her cautious statements, cited by the patent office, at the time. When \u003ca href=\"https://www.statnews.com/2015/11/06/hollywood-inspired-scientist-rewrite-code-life/\">Feng Zhang\u003c/a> of the Broad Institute and \u003ca href=\"https://www.statnews.com/2017/06/08/george-church-narcolepsy/\">George Church\u003c/a> of Harvard used CRISPR to edit genes, it was “just as we had proposed in 2012,” according to the book. She was elated that her 2012 work “inspired others to pursue a line of experimentation similar to our own.”\u003c/p>\n\u003cp>Doudna became a public scientist — she’s given a \u003ca href=\"https://www.ted.com/talks/jennifer_doudna_we_can_now_edit_our_dna_but_let_s_do_it_wisely\" target=\"_blank\" rel=\"noopener noreferrer\">TED talk\u003c/a> and 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.”\u003c/p>\n\u003cp>Her own moral journey is intriguing. She feels germline editing can be safe, and the “it’s unnatural!” argument “doesn’t carry much weight with me anymore,” she writes. “It seems to me that we’d be justified in using” CRISPR to eliminate genes that cause untold suffering, such as those for Huntington’s 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 \u003ca href=\"https://www.statnews.com/2017/02/14/national-academy-crispr-report/\">concluded\u003c/a>.\u003c/p>\n\u003cp>Doudna acknowledges, however, that “it’s difficult to see how we’d 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 Alzheimer’s, even less armpit odor — while other families muddle through with the genes nature gave them.\u003c/p>\n\u003cp>That threatens to “transcribe our societies’ financial inequality into our genetic code,” Doudna writes.\u003c/p>\n\u003cp>Her solution? “Redoubl[ing] our commitment to building a society in which all humans are respected and treated equally, regardless of their genetic makeup.”\u003c/p>\n\u003cp>\u003cem>Update, June 14: Doudna, whose office cancelled an interview with STAT before this story ran, said in an email that “positioning Martin Jinek’s role to your readers as above the work of Emmanuelle Charpentier is incorrect and unfair. Our work was conducted closely with Emmanuelle, whose contributions and insights including the role of tracrRNA in the DNA targeting complex were a key aspect of the development of CRISPR-Cas as a gene editing technology.”\u003c/em>\u003c/p>\n\u003cp>\u003cem>\u003cspan style=\"font-weight: 400\">This \u003ca href=\"https://www.statnews.com/2017/06/11/crispr-jennifer-doudna-book/\" target=\"_blank\" rel=\"noopener noreferrer\">story \u003c/a>was originally published by STAT, an online publication of Boston Globe Media that covers health, medicine, and scientific discovery. \u003c/span>\u003c/em>\u003c/p>\n\u003cp> \u003c/p>\n\u003cp>\u003c/p>\u003c/div>",
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"info": "What kind of no sabo word is Hyphenación? For us, it’s about living within a hyphenation. Like being a third-gen Mexican-American from the Texas border now living that Bay Area Chicano life. Like Xorje! Each week we bring together a couple of hyphenated Latinos to talk all about personal life choices: family, careers, relationships, belonging … everything is on the table. ",
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"info": "The Political Mind of Jerry Brown brings listeners the wisdom of the former Governor, Mayor, and presidential candidate. Scott Shafer interviewed Brown for more than 40 hours, covering the former governor's life and half-century in the political game – and Brown has some lessons he'd like to share. ",
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"info": "For decades, the process for how police police themselves has been inconsistent – if not opaque. In some states, like California, these proceedings were completely hidden. After a new police transparency law unsealed scores of internal affairs files, our reporters set out to examine these cases and the shadow world of police discipline. On Our Watch brings listeners into the rooms where officers are questioned and witnesses are interrogated to find out who this system is really protecting. Is it the officers, or the public they've sworn to serve?",
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"tagline": "Politics from a personal perspective",
"info": "Political Breakdown is a new series that explores the political intersection of California and the nation. Each week hosts Scott Shafer and Marisa Lagos are joined with a new special guest to unpack politics -- with personality — and offer an insider’s glimpse at how politics happens.",
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"possible": {
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"info": "Possible is hosted by entrepreneur Reid Hoffman and writer Aria Finger. Together in Possible, Hoffman and Finger lead enlightening discussions about building a brighter collective future. The show features interviews with visionary guests like Trevor Noah, Sam Altman and Janette Sadik-Khan. Possible paints an optimistic portrait of the world we can create through science, policy, business, art and our shared humanity. It asks: What if everything goes right for once? How can we get there? Each episode also includes a short fiction story generated by advanced AI GPT-4, serving as a thought-provoking springboard to speculate how humanity could leverage technology for good.",
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},
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"tagline": "Art is where you find it",
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"tagline": "Real stories with killer beats",
"info": "The Snap Judgment radio show and podcast mixes real stories with killer beats to produce cinematic, dramatic radio. Snap's musical brand of storytelling dares listeners to see the world through the eyes of another. This is storytelling... with a BEAT!! Snap first aired on public radio stations nationwide in July 2010. Today, Snap Judgment airs on over 450 public radio stations and is brought to the airwaves by KQED & PRX.",
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"soldout": {
"id": "soldout",
"title": "SOLD OUT: Rethinking Housing in America",
"tagline": "A new future for housing",
"info": "Sold Out: Rethinking Housing in America",
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