The FDA calls out creators of genetically tweaked hornless bulls.
- Hornless bull clones turn out to have questionable genomes.
- Scientists were so confident they didn't even look for transgenic DNA.
- No one's sure what to do with the offspring.
The arrival of Spotigen and Buri<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMTE2MTE1Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwMzUzNDgxOX0.FncQraghoKRg6Kz4tj6XS2osmzY_GroWyWTpz4jHYds/img.jpg?width=980" id="e8da5" class="rm-shortcode" data-rm-shortcode-id="b19d6c0ae8f91f802036bfab1c873ac9" data-rm-shortcode-name="rebelmouse-image" />
Image source: ANGHI/Shutterstock/Big Think<p>Recombinetics' bulls were heralded examples of gene modification's potential. Farmers regularly "poll" cows — that is, remove their horns— in a painful, difficult process aimed at preventing accidental injuries in herds and the humans that tend them.</p><p>The company used TALENs gene editing ("Transcription Activator-Like Effector Nucleases) to swap out a section of about 200 genes from a Holstein dairy bull for genes from a hornless one.</p><p>DNA editing involves cutting DNA with enzymes called nucleases targeted at the desired location in a cell's genome. Nucleases are proteins, which are hard to work with, so many researchers — including Recombinetics' — instead introduce plasmids, circular mini-chromosomes that code for the required "scissor." This causes the target cell to produce the nucleases itself, sparing the scientists the complexities of dealing with unstable protein.</p><p>In the case of Recombinetics' bulls, the plasmids also contained the replacement hornless DNA for insertion at the cut. Coming along for the ride — unknown to Recombinetics — was transgenic DNA, including the antibiotic-resistant genes and a handful of other things from a range of diverse microbes. This wouldn't necessarily have been a problem if the plasmids hadn't unexpectedly inserted themselves into the target cell's genome instead of simply delivering their payload and being done, as planned. Thus, adjacent to its edit site were <a href="https://www.independentsciencenews.org/health/gene-editing-unintentionally-adds-bovine-dna-goat-dna-and-bacterial-dna-mouse-researchers-find/" target="_blank">4,000 base pairs</a> of DNA that from the plasmid.</p>
Over-confident<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMTE2MTE2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwNDM1MTE4MX0.dfyGyeHtjCpNogRkwv3-UZHBAQ3dpFnOKtXRd-STK50/img.jpg?width=980" id="0a22f" class="rm-shortcode" data-rm-shortcode-id="4af032e6384db1af6345d8d74d1b3331" data-rm-shortcode-name="rebelmouse-image" />
Image source: wikimedia/U.S. Food and Drug Administration<p>At the time the editing was first announced, Recombinetics was very confident that what they'd produced was "100% bovine." "We know exactly where the gene should go, and we put it in its exact location," claimed Recombinetics to <a href="https://www.bloomberg.com/news/articles/2017-10-12/this-genetics-company-is-editing-horns-off-milk-cows" target="_blank">Bloomberg</a> in 2017. "We have all the scientific data that proves that there are no off-target effects." In response to the latest findings, however, Tad Sontesgard of the Recombinetics subsidiary that owns the animals, admitted, "It was not something expected, and we didn't look for it." He acknowledges a more thorough examination of their work "should have been done."</p><p>Since genetically edited animals may be consumed, the FDA's position is that they likely require thorough testing and approvals. Recombinetics has publicly complained about such hurdles standing in the way of making animal genetic editing a routine occurrence. (They've also developed piglets that never hit puberty.) The company attempted to <a href="https://www.technologyreview.com/s/610027/farmland-gene-editors-want-cows-without-horns-pigs-without-tails-and-business-without/" target="_blank">convince the Trump Administration</a> to take genetically altered animals away from under the FDA.</p>
How the problem was found<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMTE2MTE2NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyMDA3NzAyMX0.SBCvmAAsWaDYU7dkPQ7CgcrtQovHK-MWvOizZUCZqQg/img.jpg?width=980" id="43f50" class="rm-shortcode" data-rm-shortcode-id="6f28fb809a618ce4383b7cb4942805fb" data-rm-shortcode-name="rebelmouse-image" />
Image source: Moving Moment/Shutterstock<p>Not surprisingly, Recombinetics never applied for approval with the FDA, but Alison Van Eenennaam, their collaborator from University of California, Davis, did inform the FDA of their existence to facilitate exchanges of research insights and data.</p><p>Since the surviving edited cattle were being put up at Davis, Eenennaam started thinking about what to do with them. Incinerating experimental animals — and each of these weighs about a ton — costs 60 cents per pound. On the other hand, turning them into hamburger and steaks could reverse that cash flow. Her attempt to win the cows a food exemption from the FDA led to the discovery of the plasmids, though Sontesgard <a href="https://www.technologyreview.com/s/614235/recombinetics-gene-edited-hornless-cattle-major-dna-screwup" target="_blank">asserts</a> they'd be safe to eat in either case.</p><p>And then there's milk. Brazil agreed to raise the first herd of genetically modified hornless dairy cows. Regulators there had even determined no exceptional oversight was going to be required.</p><p>Soon a bioinformatician from the FDA stumbled across the plasmid in a bull's genome. It's estimated that about half of Buri's 17 offspring also have it in theirs. The cows are now absolutely classified as genetically modified organisms, GMOs, not pure cow. Brazil has backed out.</p>
Slowing their roll<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMTE2MTE2OC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwNzcxMDgxMn0.VmwCM6ss3JJ0-imNVggLLjNviBpY5KhHIuz7CtxvaMs/img.jpg?width=980" id="22429" class="rm-shortcode" data-rm-shortcode-id="0ad6c70f0e27fe6d94516a01cb5fb35f" data-rm-shortcode-name="rebelmouse-image" />
Image source: Sergey Nivens/Shutterstock<p> As science moves forward a few steps, it often has to back up a step or two. Glimpsing a solution, especially to such a complex problem as genome editing, isn't the same as having one fully in hand, no matter how attractive the reward of getting there first may be, or how much money is to be made. We're on the edge of a new frontier here, and there are a growing number of similar tales. Scientists do need courage to stretch the boundaries of the known, yes, but humility is also a good idea.</p>