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Will Latest CRISPR Uses be Game Changers in the GM Debate?

By Tabitha M. Powledge

Two papers published in the last week were signal events for agricultural genomics. First was the draft of the huge, and hugely complex, genome of bread wheat, the staff of life for 30 percent of humanity. The other, from Chinese scientists reporting advanced gene editing of bread wheat to make it resist the fungal pathogen powdery mildew, claims to have brought us a technical method for reducing the political battles over GMOs–genetically modified organisms.

I’m doubtful, but let’s see.

I wrote about the bread wheat papers in my Tuesday column for the Genetic Literacy Project. I won’t recap much here, except to note that wheat’s promiscuity over the past several hundred thousand years is unusually wanton even in the permissive plant Kingdom. The more-than-usually incestuous result has been bread that tastes heavenly but has made the work lives of genome sequencers hellish.

Unlike corn crops, where it’s nearly impossible to find examples that are not GMOs, almost no wheat is genetically engineered. Agricultural researchers are excited about the wheat genome project because having even a draft version will be a big help to conventional breeding.

There are good reasons to bestow new traits on wheat. Not just disease resistance, as in the Chinese example, but especially resistance to drought. Wheat needs to be better equipped for the hotter, drier planet our descendants will have to live with.

Comment on the powdery mildew paper has centered on the its methodology: CRISPR (clustered regularly interspersed short palindromic repeats), which can be viewed, the commentators say, as a natural process. A sort of mutation. CRISPR, one of Science‘s “Breakthroughs of the Year” in 2013, is a trendy darling just now. At Gene Expression, Razib Khan wrote in March, “This may indeed be a world-turned-upside-down moment, and CRISPR may finally cash out the promise that biological science is going to result in a flowering of engineering analogous to what occurred during physics’ ‘atomic age.’”

And what is CRISPR?

CRISPR is a new genetic engineering method, one of a group often called advanced gene editing. It is based on a kind of adaptive immune system that bacteria invented three billion years ago. Bacteria remember the viruses that have infected them and put together a targeted molecular defense so that the next time the same virus comes around, it is cut up and killed.

The CRISPR enzyme (green and red) binds to a stretch of double-stranded DNA (purple and red), preparing to snip out the faulty part. Credit: Jennifer Doudna/UC Berkeley

The CRISPR enzyme (green and red) binds to a stretch of double-stranded DNA (purple and red), preparing to snip out the faulty part.
Credit: Jennifer Doudna/UC Berkeley

CRISPR makes possible targeted modifications of almost any gene. Specific genes can be turned off, turned on, and/or edited. The potential applications of  the CRISPR system can hardly be overstated. And it is simpler and cheaper than any other current approach to genome modification.

Irresistible. I described what CRISPR is and how it works and what its future holds–a lot of intriguing and possibly scary stuff, including genetic modifications of Homo sap–in a column I wrote for GLP in February. That piece was triggered by a paper reporting on using CRISPR to create monkey infants with genetic changes.

The Chinese work on powdery mildew in wheat was a (relatively) simple use of CRISPR. The researchers used it to disable three wheat genes that make wheat more vulnerable to the fungus. They inserted no foreign genes.

In a Technology Review post about the research, David Talbot quoted Xing-Wang Deng, who heads a joint research center for plant molecular genetics and agricultural biotech at Peking University and Yale. “And this could be considered as a nontransgenic technology, so that can be very significant. I hope the government would not consider this transgenic, because the end result is no different than a natural mutation.”

CRISPR for genetic modification of wild populations and whole ecosystems?

But other potential uses of gene editing go way beyond natural mutation. At a SciAm Guest Blog last week, Kevin Esvelt, George Church and Jeantine Lunshof urged the use of gene editing “to alter not just domesticated species, but entire wild populations and ecosystems.” They want to edit mosquito DNA to make the insects more resistant to infection by malaria parasites–and thus unable to transmit malaria to people. Another proposal is to return herbicide-resistant weeds to their natural vulnerable state.

Carl Zimmer explained and explored this proposal for mosquito modification in his New York Times column, quoting other scientists who worry that the plan is risky. Church and colleagues say that devising regulations before such a project is launched would reduce the risks, and so would coming up with a Plan B for what to do in case something goes wrong.

In my February column about CRISPR, I described its potential applications for gene therapy, for the study of gene functions, for making epigenetic modifications that can turn genes off and on in precise ways, for “smart bombs” that can target disease-causing bacteria without harming benign bugs, and for making genetically modified animals. That includes attempts at improving humans.

Gene editing may not use traditional biotechnology tools for genetic modification, but it could speed up the process of rewriting genomes–our own included. Do these seem to you like projects that GMO opponents will not oppose because the methodology is novel? They strike me as examples of what my former philosopher colleagues would have called a distinction without a difference.

My guess is that anti-GMO activists are likely to see in these techniques the same potential outcomes that have always driven them nuts, outcomes like control of must-have crop varieties by agribusiness conglomerates and unpredictable disastrous ecological consequences. It’s hard to imagine they will be converted to the cause of genetic modification because the methodology is based loosely on a technique bacteria evolved billions of years ago.

Tabitha M. Powledge is a long-time science journalist, book author and media critic whose work has appeared in popular publications, including Scientific American, Popular Science, Health, Salon.com; and scholarly journals, including:  The Lancet, Current Biology, PLOS Biology, and Nature Medicine. In previous incarnations, she ran the Genetics Bioethics Group at the Hastings Center, served as a Senior Editor at Nature Biotechnology, and was Founding Editor of The Scientist.

This post was originally published (July 25, 2014) in On Science Blogs – a blog hosted on the PLOS BLOGS Network. In On Science Blogs Tabitha Powledge offers a weekly roundup of research being discussed by leading science bloggers. Original title:  “A Fix for GMO Battles?…”.

  1. Tabitha:

    One only need to look at the emergence of opposition to synthetic biology to see your hypothesis is correct. It appears to be genetic modification per se rather than a specific methodology. The fundamental narrative seems to be” “though shall not tinker with that which is “”natural”” in the service of commerce.” Further just to be “safe” do not deploy in the service of public health or preventative medicine either.

    The romanticization of the “natural” (or from the conservative side “that which God intended”) places science in the position of being a threat to natural systems and/or a purveyor of immoral acts.

    I prefer to think science is using these gifts of talent for the improvement of health, but that view is not shared, as you suggest.

  2. Yeah, I think you’re right. It’s the “natural” thing that people seem to be worried about. I don’t know why that worry about interfering with nature doesn’t apply equally to the conventional breeding techniques Homo sap has employed for >15,000 years (if you count dogs.) But it doesn’t seem to. Odd.

  3. “Church et al’s idea” of genetically modifying insect populations such as mosquitoes has been in the insect research community since the 1960s (search George Craig for a start) and considerable effort and progress has been made on a number of fronts to date – without CRISPRs.

    Certainly CRISPRs provide insect biologists a new tool for exploring ideas of population replacement, modification or eradication using genetic tools.

    Take a look here for a very recent example of a real ‘drive system’ that can eradicate or reduce human malaria vector populations.


    David O’Brochta, Ph.D. for IGTRCN.org

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