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Scientists to Engineer Hornless Dairy Cows

Scientists to Engineer Hornless Dairy Cows



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Holstein cows to lose their horns to gene editing

Wikimedia/Gnagarra

A herd of cows blandly chewing their cud in a grassy field seems like an unlikely source of danger, but the pastoral scene apparently has a dark side, so scientists are now trying to genetically engineer some hornless dairy cows.

According to the Daily Mail, removing the horns from dairy cows would cut back on the risk of injury to farmers and other animals. Farmers currently burn off the horn buds of baby cows to prevent horns from developing, but the process is unpleasant and painful for the animals. Farmers were previously able to get rid of the horns on some varieties of beef cattle through selective breeding, but have been unable to do the same for dairy cows without affecting the milk supply.

Instead, scientists are going to take a crack at it. Researchers plan to achieve hornless Holsteins, the highest-producing breed of dairy cow, by taking a bit of DNA that is known to stop horn growth from other breeds of cattle and editing it into the Holstein genome.

Scott Fahrenkrug, professor of genetics at the University of Minnesota, has already taken the horn-suppressing DNA and edited it into cells taken from a Holstein bull named Randy. Next, those cells will be turned into 40 embryos and implanted into a herd of female Holsteins. One gestation period later, those cows will give birth to little clones of Randy that don't have horns. The offspring of the hornless Randy clones will also be hornlesss. The scientists say the process will not have any effect on the milk the new cows will produce, because aside from the missing horns they will be just like regular Holstein cows.


Hornless cattle will herald a gene-editing revolution on farms

TO THE casual eye, they look no different to other dairy cows. But where most dairy cows have scars from where their horns have been removed, these have none. Thanks to a tiny tweak to their DNA, they will never grow horns.

Created by a Minnesota-based company called Recombinetics, the hornless cattle are the first of a new wave of farmed animals developed using techniques that, unlike conventional genetic engineering, involve no “foreign” DNA (see “How to tweak a genome“).

“We already have numerous cattle in more than one location,” the founder &hellip


Regulatory 're-think'

The latest work was carried out to determine whether the genome edit had been faithfully passed on to one of the bulls' offspring - and to look for any unexpected changes.

The researchers sequenced the genomes (the full complements of DNA stored in the nuclei of animal cells) of the calves and their parents for analysis.

This showed unequivocally that the genome-edited traits had been passed on to the calves.

The use of genetically engineered animals could revolutionise whole areas of public health and agriculture, according to advocates. But is the world ready for modified mosquitoes and GM salmon? Read the feature

A short stretch of bacterial DNA called a plasmid, used to deliver the hornless genetic variant to the parent bull, had been incorporated alongside one of the two hornless genetic variants.

Dr Van Eenennaam said the plasmid does no harm to the animals, but its inclusion technically makes the genome-edited bull a genetically-modified organism (GMO) in the traditional sense, because it contains foreign DNA from another species.

The researchers found no unintended genetic alterations in the calves.

Since the original work to produce the hornless cattle, which was initiated by Minnesota-based biotech company Recombinetics, new methods have been developed that no longer use plasmids or any other foreign DNA sequence.

Some scientists see the advent of genome editing as an opportunity to re-think the current US regulatory regime surrounding genetically modified animals.

The process for getting genetically modified food animals to market is regarded as costly and long by those involved in the field. So far, only one genetically modified animal has successfully navigated the regulatory approval process - the AquaAdvantage salmon.

These salmon incorporate a gene that allows the modified animals to grow all year round, rather than just during spring and summer. However, the process of regulatory approval by the Food and Drug Administration took more than a decade and cost millions of dollars.


5 ways CRISPR-engineered animals can help combat climate change

Climate change is a man-made problem, but humans aren’t the only animals that will be impacted by warming temperatures and shifting weather patterns. Climate change threatens many coral reefs and other native species, fish and livestock. Scientists are working to address these issues by adapting the gene editing technology known as CRISPR for use in animals.

1. CRISPR-engineered coral reefs

Coral reefs are threatened by many anthropogenic activities, but the effects of climate change are especially potent. Heat waves have already killed half of the coral in the Great Barrier Reef. Scientists have been trying to breed coral for improved heat tolerance, but corals are finicky breeders. Corals also only spawn once per year. That’s a small window. What’s worse, successfully transferring a desirable trait could take several breeding cycles. But the reefs do not have years to wait.

Coral scientists needed a way to speed up evolution to keep pace with the fast changing climate. Last spring, Stanford, the University of Texas, and the Australian Institute of Marine Science teamed up to demonstrate, for the first time, that it’s possible to tweak genes in coral using CRISPR.

2. Protecting livestock with CRISPR

The current climate creates natural barriers that prevent the spread of diseases and the animals that carry them. Climate change will cause weather patterns to shift and with that, the boundaries of some pathogens will shift as well. Since bacteria and viruses tend to fare better in warmer climates, this shift will likely not be a positive one.

As the playground for diseases expands, animals, including livestock, are likely to become threatened by diseases in areas where those diseases were not previously an issue. Fortunately, scientists are already using CRISPR to engineer disease resistance in several livestock including cows, pigs and chickens.

3. CRISPRing cows to produce less methane

We’ve all heard those stats about how cow belching is worse for the environment than cars. Those claims are overblown, but cows really do produce a lot of methane and that methane is not helping with climate change.

Veterinary researchers at the University of Adelaide recently showed that how much methane a cow produces very much depends on that cow’s genetic makeup. That means that genetic engineering could help shrink the big burpers’ carbon hoofprint. CRISPR has already been used to tweak other traits in cows, so methane emission could be a next step.

4. CRISPR helps animals take the heat

Not only will diseases increasingly threaten livestock as a result of climate change, but the rising temperature itself is also a direct threat. Extreme heat can be dangerous for livestock living out in the elements.

Cattle living in the tropics have adapted to high temperatures by evolving a gene called Slick. The Slick gene gives cows shorter hair. In the future, CRISPR could be used to help spread this trait to cattle in regions that will become unbearably warm.

5. CRISPR for aquaculture

Rising ocean temperatures mean that coastal fish will be among the animals most severely impacted by climate change. The threats of climate change on fish are exacerbated by offshore aquaculture that can spread diseases between farmed and wild populations. In addition to an ecological risk, climate change threatens communities that depend on fish for their food and economy.

One potential remedy to threatened fish populations is to move aquaculture farms on shore, where they cannot mix with wild fish and the water temperature can be more carefully controlled. Decoupling fish farms from coasts can also help bring the fish market closer to consumers, thus decreasing the environmental costs associated with transporting seafood.

In order for landlocked aquacultures to be economically viable, fish need to reach market weight faster than they do in ocean cages. Older genetic engineering techniques have been used to develop faster-growing salmon, and landlocked salmon farms are now a reality. Researchers are now looking to CRISPR to prepare other fish species for aquaculture.

The regulatory landscape for CRISPR-engineered animals

When it comes to using CRISPR in animals, the regulatory landscape is much more complicated than it is for plants or microbes. The only genetically engineered animal that has been approved by the FDA for consumption thus far had to overcome the same regulatory hurdles as a veterinary drug. These animals (AquAdvantage salmon) are transgenic, that is, they contain a Chinook salmon gene not naturally present in that species.

CRIPSR can be used to make much more subtle changes to the genome, changes that could have occurred through natural mutations. For this reason, the USDA has elected not to place any additional regulations on CRISPR-edited plants. This will not be the case for animals.

The FDA has indicated it will regulate CRISPR-engineered animals in the same way it has historically regulated transgenic animals — as if they are veterinary drugs. Scientists argue that these regulations will likely stall the progress and impact of CRISPR research.


A Cow, a Controversy, and a Dashed Dream of More Humane Farms

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Photograph: CHRISTIE HEMM KLOK

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On the morning of August 7, Alison Van Eenennaam awoke to a tweet from a man she had never met. He had sent her a link to a story written in German, illustrated with a clip-art cow next to an udder-pink biohazard symbol. “Aren’t you involved in the hornless cows criticized here by a German NGO?” the man tweeted at Van Eenenaam from nine time zones away. “Can you give us some details on what @US_FDA found?”

Van Eenennaam could not. But not because she didn’t have the details.

For nearly two years the animal geneticist and her team at UC Davis had been meticulously poking, prodding, weighing, and measuring a herd of six young, genetically dehorned Herefords. Born on campus in September of 2017, the calves were gene-editing royalty. Their father, Buri, had been created in a lab in Minnesota a few years before, his genome tweaked by the agtech startup Recombinetics to prevent him from growing horns. Horns are considered a menace in the commercial dairy business and typically get burned off, so the startup had set out to use engineering to make a more humane livestock industry.

A world-first, he and his half-brother Spotigy were an overnight media sensation. “We know exactly where the gene should go, and we put it in its exact location,” Recombinetics executives told Bloomberg in 2017. That year, Van Eenennaam secured a half-million-dollar grant from the US Department of Agriculture to see if Buri’s descendants would inherit his genetic alteration as intended, and to study those animals’ health and dairy-producing potential. (Spotigy was sacrificed in 2016 to analyze his meat for quality. He did not sire any calves.)

So as she stared at Twitter on that recent August morning, Van Eenennaam knew more than anyone about Buri and his extended family. Including the fact that six months before, scientists at the US Food and Drug Administration had stumbled upon a surprise in Buri’s DNA. There had been an accident during Recombinetics’ editing process. And the mistake had been passed down to four of Buri’s six calves, along with the hornless gene. Yet those calves were every bit as healthy as their naturally horned Hereford counterparts, as far as she could tell.

But she couldn’t talk about any of that because she had submitted a paper on it to a journal for peer review. If she discussed it now, her paper could get rejected. So she seethed to herself as she read a line in the German story: “No research has been carried out on the possible consequences for animal health, or whether these additional genes are biologically active.”

Research takes time, especially when it involves animals with a nine-month gestation period. By the time those results get published, the study is in a sense old news. It looks back at the long story of a scientific discovery, like peering at ancient starlight through the barrel of a telescope. In the age of the internet, scientists have grown increasingly impatient with the plodding pace of traditional publishing and sought to shake it up. For the most part, these growing pains have remained cordoned off in conference proceedings, invisible to the general public. But sometimes, clashes in publishing culture can spill over into the real world in unexpected ways, shaping public opinion with wide-reaching effects. In the case of the hornless cows—the would-be poster calves of the future of food—it would turn their story upside down.

Van Eenennaam moved from Melbourne, Australia to Davis, California right as genetic engineering was transforming the agricultural college town. In nearby fields the Flavr Savr tomato was making its way out of the ground and into local grocery stores, to become the first genetically modified food available for purchase.

She and other young faculty decided to harness these new genetic engineering tools to do for livestock what other researchers and companies were doing for crops—giving animals and the foods they produced new traits. They embarked on experiments in cattle and goats to make their milk more nutritious. But then their work hit a snag. The FDA decided that introducing foreign DNA into animals qualified them as veterinary drugs, creating a lengthy and costly approval process that dissuaded many scientists. Funding for transgenic livestock research foundered. And people like Van Eenennaam scraped by on the few remaining grants.

Then came the gene-editing revolution. Tools like TALENS and Crispr, which allow scientists to alter animals’ genomes without adding foreign DNA, reignited livestock researchers’ imaginations and spurred a new crop of companies, including Recombinetics. Its engineers wanted to introduce DNA from hornless, non-dairy cattle breeds into their milk-and-cheese producing cousins. The company sought out Van Eenennaam to help house and study its creations. In 2015, Buri and Spotigy moved to UC Davis.

A year and a half later, Buri’s sperm was used to artificially inseminate ten horned Hereford dams in the Davis herd. When Van Eenennaam got word that six pregnancies had been confirmed, she sent in an application to the USDA Biotechnology Risk Assessment Grant program. Its mission is to fund projects that help federal agencies evaluate emerging technologies. Van Eenennaam was cautiously optimistic that by collecting reams of data on the calves, her team might help make a case for gene-edited animals to be regulated differently than transgenic ones.

Those hopes didn’t last the month.

On January 19, 2017 the FDA issued a set of draft guidelines, lumping gene editing together with older GMO technologies. The USDA, which oversees gene editing in plants, has decided, in most cases, to not regulate the technology, treating it as a sped-up version of traditional breeding methods. But the FDA reached a different conclusion, that the editing process presents unique risks. What if Crispr or TALENS make changes they’re not supposed to make? What if those mistakes result in unexpected mutations? And what if those genetic changes spread from livestock to their wild relations?

“We were right in the middle of doing our experiments and it caught us off guard,” says Van Eenennaam, who has not been shy about criticizing the FDA’s decision. “We had predicated everything on assuming those animals could go into the food supply.”

If the calves—five males and one female—were considered GMOs, they couldn’t be butchered and sold off through the University’s Meat Lab. For Van Eenennaam, that was key to making the economics of her research work out. Instead, each 2,000 pound animal would have to be incinerated, at a cost of 60 cents per pound. So Van Eenennaam petitioned the FDA for an exemption.

In December 2018, she sent the agency a detailed dossier on the calves—disclosing the results of their physical exams, blood tests, and DNA sequencing. Based on her team’s analyses, nothing looked amiss. The animals appeared healthy, their genomes precisely edited, their furry foreheads completely horn-free. While Van Eenennaam waited for the agency to make its decision, she and her colleagues wrote up their results, and in February submitted them to Nature Biotechnology.

While the UC Davis team typed up their manuscript, scientists at the FDA were combing through the data too. One of them was Alexis Norris, a biostatistician in a division of the Center for Veterinary Medicine. When she joined the agency in July 2018, she hadn’t had much experience with the genomes of cows and pigs and other barnyard species. But she’d gotten really good at analyzing massive amounts of sequence data as part of her graduate and post-graduate work at Johns Hopkins, on the genetic underpinnings of human diseases. At the FDA, she was putting those skills to use screening livestock DNA data for unintended edits.

Part of her work involved developing software specific to that task. Norris’s team had long been planning to test-drive it with the genomes of Buri and Spotigy, because theirs was the largest publicly available dataset for a gene-edited animal. “We wanted to make sure it could handle that size data,” says Norris. “And that our computer wouldn’t crash while analyzing it.”

Earlier this year, they used their software to compare Buri and Spotigy’s DNA to a reference bovine genome. Then, as an extra precaution, they also checked the cow’s DNA against a short sequence of circular bacterial DNA called a plasmid. Recombinetics had used this particular plasmid to ferry the genetic instructions for hornlessness into the cells that would later become Buri and Spotigy. It isn’t supposed to stick around. But neither Recombinetics or Van Eenennaam had ever checked to ensure that was true.

As the FDA’s software began to spit out results, Norris saw the hornless gene, right where it should be. But then, next to it, she saw sequencing data that matched the plasmid. “This was a very unexpected finding,” says Norris. What was supposed to be a quick validation had turned up a major surprise. During the editing process, Buri and Spotigy had accidentally acquired a bit of bacterial DNA. It wasn’t much, about 4,000 letters. But the genetic insertion was enough to make the bulls GMOs by any definition.

It took a few weeks for Norris and her team to feel confident they’d made a real discovery and not stumbled on, say, a flaw in their code. On March 6, they broke the news to Van Eenennaam and her collaborators. According to Van Eenennaam, the FDA revealed the plasmid hadn’t only slipped into Buri and Spotigy’s DNA. It had also been passed down to four of Buri’s six calves. (The FDA declined to comment on the calves, citing confidentiality agreements.)

For Recombinetics, the fallout was swift. The company had crafted a deal with Brazil to start a hornless herd there after government officials determined the company’s cows didn’t require special oversight. The company was readying shipments of Buri’s sperm for export when the FDA alerted its Brazilian counterparts about the bacterial DNA glitch. The Brazilian agency soon re-classified Buri (and any of his progeny) as a GMO product. Recombinetics abandoned the project, as WIRED exclusively reported in August, but the company has plans to revisit it in the future with a plasmid-free cell line.

Meanwhile, Van Eenennaam’s team notified Nature Biotechnology of the discovery. Then they went over the calves’ genomes themselves to confirm the presence of bacterial DNA, and sent their results to the journal. During this time, Norris and her FDA colleagues were also busy writing up their findings. The plasmid discovery had been theirs, after all, and they didn’t want other people to make the same mistake. They included in it another potentially incendiary detail: The cows’ bacterial DNA contained a few unwelcome genes for antibiotic resistance. In July, they uploaded a summary of their work to the preprint server bioRxiv, a somewhat controversial repository for manuscripts that have not yet been peer-reviewed. While hailed by many as a crucial tool for accelerating scientific progress, critics worry that preprints, which are meant to be consumed by fellow scientists, might be misinterpreted by the general public.

The study went largely unnoticed until it was picked up in early August by a German organization called Testbiotech. That’s how Van Eenennaam first learned of the FDA publication. Other stories quickly followed on other anti-GMO platforms. Soon her email inbox and Twitter timeline filled with questions and media requests to comment on the preprint. She grudgingly swatted them all away. Because Nature Biotechnology was still reviewing her manuscript, she couldn’t tell people the small success stories embedded in all this mess: that two of the young bulls had successfully inherited the hornless gene with no bacterial DNA that they were healthy and hornless and that with proper screening, making more like them would be easy. But as the weeks passed and the anti-gene-editing rhetoric ratcheted up on social media, she despaired that public sentiment was turning against the cows.


Scientists to Engineer Hornless Dairy Cows - Recipes

There are only a few cattle breeds in existence that have no horns naturally but now American scientists are developing the trait within Holstein cattle.

Horned animals provide a threat to other animals, farmers and dog walkers and only a handful of breeds such as Aberdeen Angus and Hereford have no horns. However, scientists in California have come up with a way to splice the &lsquohornless&rsquo gene from the Angus breed into the Holstein dairy breed in a move they say will make farming safer.

Animal geneticist Dr Alison Van Eenennaam, of the University of California, discovered it is possible to splice the &lsquohornless&rsquo gene from Aberdeen Angus cattle into the black-and-white Holstein dairy cows so that they are born without protrusions. Calves from dairy breeds and most other beef breeds normally have to be dehorned days after birth which can be quite a traumatic experience for them.

Breeding hornless cows would also make it easier to sort them into pens and trucks, potentially saving the industry millions of pounds a year. However, there is a glitch as effectively these cattle are classed as being genetically modified. Due to this fact, these newly bred cattle will not be arriving anytime soon as regulators have not agreed that genetically engineered animals can be allowed in the food chain.

The first calves, which were created using IVF techniques, are called Spotigy and Buri and the team at the University of California are hoping that their offspring will also be hornless even if they are bred with horned cows.

If successful, it will allow the industry to bypass decades of breeding hornless cows.

The team of scientists at the University of California are also hoping to perfect a technique to genetically design cattle so that they only produce male offspring, which grow faster than females.

And, they hope to engineer cows which are less prone to pneumonia, which would reduce their need for antibiotics.


Breeding safer hornless Holstein cows

There are only a few cattle breeds in existence that have no horns naturally but now American scientists are developing the trait within Holstein cattle.

Horned animals provide a threat to other animals, farmers and dog walkers and only a handful of breeds such as Aberdeen Angus and Hereford have no horns. However, scientists in California have come up with a way to splice the ‘hornless’ gene from the Angus breed into the Holstein dairy breed in a move they say will make farming safer.

Animal geneticist Dr Alison Van Eenennaam, of the University of California, discovered it is possible to splice the ‘hornless’ gene from Aberdeen Angus cattle into the black-and-white Holstein dairy cows so that they are born without protrusions. Calves from dairy breeds and most other beef breeds normally have to be dehorned days after birth which can be quite a traumatic experience for them.

Breeding hornless cows would also make it easier to sort them into pens and trucks, potentially saving the industry millions of pounds a year. However, there is a glitch as effectively these cattle are classed as being genetically modified. Due to this fact, these newly bred cattle will not be arriving anytime soon as regulators have not agreed that genetically engineered animals can be allowed in the food chain.

The first calves, which were created using IVF techniques, are called Spotigy and Buri and the team at the University of California are hoping that their offspring will also be hornless even if they are bred with horned cows.

If successful, it will allow the industry to bypass decades of breeding hornless cows.

Dr Van Eenennaam said: “Gene-editing is a technology that can seamlessly combine the desired traits of two unrelated animals without crossbreeding, thus preserving the present day production from dairy cattle while eliminating horns with genetic methods.” For now, the experimental cows produced by the University of California cannot yet be used in farming. “It’s not yet clear what regulatory status food-animals produced with gene editing will have,” added Dr Van Eenennaam.

“The prospect that gene-edited animals would be subject to regulation as an animal drug, even though their genetic modifications might be indistinguishable from those obtained through conventional breeding, is a concern for animal breeders who see the potential to employ genome editing to complement traditional genetic improvement programs.”

The team of scientists at the University of California are also hoping to perfect a technique to genetically design cattle so that they only produce male offspring, which grow faster than females.

And, they hope to engineer cows which are less prone to pneumonia, which would reduce their need for antibiotics.


Media mangles latest biotech innovation—hornless cows

It’s always revealing how the press portrays the latest development in agricultural genetics—soberly or with the rush of hysteria that has come to define media coverage of biotechnology.

Unfortunately, a series of reports over the weekend about advances in the development of a dairy cow genetically tweaked to be hornless were tinged with familiar exaggerations and distortions. “Scientists are designing a health and safety cow, genetically altered to have no horns,” claimed the Sunday Times. “Hornless ‘Frankencow’: Genetic engineers aim to create super-bovine,” shouted Russia Today. Geneticists, they say, are “extracting” a strip of DNA from the genome of one cattle and “implanting” DNA it into another. A stream of stories as outlined The Daily Telegraph and a slew of other news outlets read like pages from the anti-GMO playbook. The stories are liberally sprinkled with code words about designer animals, transgenics and Frankencows. No wonder people are in a tizzy.

Actually, the innovations that led to the hornless dairy cow are both breathtaking and simple—part of an international effort that has found a less expensive, faster, safer and more precise way to combine genetic engineering with standard breeding techniques to modify livestock. It’s an advance, not a revolution. Scientists in the United Kingdom and the United States are partnering to develop a classic farm animal—hornless dairy cows so cattle will not endanger humans, themselves and other animals in the vicinity of their swinging heads.

Polled livestock—animals without horns in normally horned species—have been around for ages. Note this article (at left) from 1947 describing a farmer in Iowa who had developed a herd of hornless Guernsey cattle, bringing his total of polled cattle to 16, all descendants of the original stock.

While farmers have been able to crossbreed beef cattle, such as Aberdeen Angus, so they do not have dangerous horns, they’ve had less luck in the most productive dairy breeds, particularly Holsteins, the world’s highest producing dairy cow.

Could biotechnology lend a hand here? Scott Fahrenkrug, a professor of genetics and the University of Minnesota believes it could. Teaming with scientists at Texas A&M University and the University of Edinburgh, Fahrenkrug founded a company, Recombinetics, that uses “molecular scissors” dubbed TALENs to move around natural snippets of DNA found in animals. Fahrenkrug’s technique does not involve transgenics, which results from moving genes from one species to another. While utterly safe, the very mention of genetic manipulation enrages anti-GMO activists. In this case, Recombinetics is mirroring nature—taking snippets of DNA that first appeared through natural, spontaneous mutations in livestock hundreds of years ago to create hornless cows. The snippets are copied—not inserted as various reports had it. They are not moved. No “foreign” DNA is inserted. We’ve been eating these cows and drinking their milk for centuries—so we are sure there are no adverse health consequences.

“The mutation is totally natural and clearly safe,” Fahrenkrug told me. “We could move this mutation crudely through cross-breeding. But since the 1960s, we have had a 10-fold increase in milk production. If we had to create these hornless dairy cows by these old-fashioned techniques, it could take years and at best it would result in a mix-up of the beef and milk stocks. They would devastate both lines. The other alternative is what we choose to do it. Let’s do it precisely, protecting the health and integrity of the animals and guaranteeing a robust beef and milk lines.”

So, here we have a technique that is not transgenic, as most news articles implied. No “foreign” DNA is inserted, as many reports had it. No genetically modified organisms (GMOs) were created. Yet when you read the reports—or worse, the comments posted by activists—you would think Mother Nature had been violated.

Progressives and sustainability experts should be eagerly promoting and embracing Fahrenkrug’s editing technique, which would mean that fewer cows are manually dehorned on farms, a much more invasive and painful process. “This would be a major advance in animal welfare,” said Geoff Simm, a professor of animal breeding who chairs the UK government’s Farm Animal Genetic Resources Committee, and has long championed the idea. People for the Ethical Treatment of Animals has expressed tentative support for this innovation, noting it would have a dramatic and positive impact on the lives of livestock. But more uncompromising groups, such as the American Anti-Vivisection Society, remain opposed to it on the grounds that it might make factory farming, which is their central target, more acceptable.

The beauty of Fahrenkrug’s work is that scientists are using what are essentially classical breeding techniques, albeit more precisely and without the use of antibiotic resistance genes (one of the main targets of anti-GMO campaigners). The process mimics natural genetic mutations so closely that it would be impossible to tell from examining the animal’s DNA whether or not it had been altered, researchers say.

Creating hornless milk cows is just one of the cutting edge projects using this editing technique. Fahrenkrug is using similar techniques to develop pigs and cows that are resistant to hoof and mouth disease. He’s also pioneered the development of “sustainable cows”—animals that grow larger yet consume less protein and also give off less gases released as methane waste, which could dramatically cut down on greenhouse gas levels. He’s also identified ways to knock out a disease carried by as much as 25 percent of Jersey cows simply by editing out a single letter in the 3 billion bovine genetic alphabet.

Professor Bruce Whitelaw, Fahrenkrug’s partner at the Roslin Institute at the University of Edinburgh, calls these advances “clean genetic engineering” for how precise and safe it is, thanks for the fact that it uses existing mutations—yet that distinction is lost on anti-GMO campaigners who paint biotechnology with a broad brush. “Unless you had an audit trail of how that animal was formed, you would have no way of knowing how that mutation happened. It could have happened naturally, or in this case been engineered by a DNA editor.

Most anti-GMO campaigners, baffled by the simplicity of Fahrenkrug’s technological breakthroughs, continue to mischaracterize his work and similar biotechnology, breakthroughs by widely circulating the “Frankencow” canard. It’s not just campaigners, however, Fahrenkrug notes. He pointed to a central clause in the “Genetically Engineered Food Right to Know Act,” introduced in Congress last week. The wording was clearly guided by activists rather than scientists, he told me. For example, the bill now uses a sweeping and very unscientific definition of “genetic engineering” to include “in vitro nucleic acid techniques, including recombinant DNA and direct injection of nucleic acid into cells or organelles.” That’s stunning in its breadth … and would result in mandatory labeling of natural processes, such as those introduced by Fahrenkrug. In effect the poorly written legislation attempts to re-classify some simple techniques used in classical breeding as GMOs—and could in the process endanger the technologically enhanced classic breeding techniques that are poised to revolutionize animal welfare. However intended, that’s just one of many passages in this shabbily written bill that will retard or kill the biotechnology revolution.

If passed in its current form, this bill could undo progress in our science-based regulatory system and unnecessarily complicate the marketing of natural and safe products springing from Fahrenkrug’s and others pioneering work in gene editing. This backwards thinking in the Era of the Genome would tragically hinder the development of foods focused on sustainability, feeding the burgeoning world, and enhancing animal welfare.

Jon Entine, executive director of theGenetic Literacy Project, is a senior fellow at theCenter for Health & Risk Communication andSTATS (Statistical Assessment Service) at George Mason University.


Scientists genetically engineer hornless dairy bulls

The technology has been proposed as an alternative to debudding, a common practice performed to protect other cattle and human handlers.

This process can, however, often be unpleasant and has implications for animal welfare.

Now researchers at the University of California, Davis, have successfully bred bulls without horns after splicing the ‘hornless’ gene from Aberdeen Angus cattle.

They inserted this gene into the Holstein breed. Since then, the team have been studying six offspring of a dairy bull, genome-edited to prevent it from growing horns.

They report that none of the bull’s offspring developed horns, as expected, and blood work and physical exams of the calves found they were all healthy.

The researchers also sequenced the genomes of the calves and their parents and analysed these genomic sequences, looking for any unexpected changes.

“Our study found that two calves inherited the naturally occurring hornless allele and four calves additionally inherited a fragment of bacterial DNA, known as a plasmid,” said author Alison Van Eenennaam, with the UC Davis Department of Animal Science.

Plasmid integration can be addressed by screening and selection, in this case, selecting the two offspring of the genome-edited hornless bull that inherited only the naturally occurring allele.

“This type of screening is routinely done in plant breeding where genome editing frequently involves a step that includes a plasmid integration,” she added.

Van Eenennaam said the plasmid does not harm the animals, but the integration technically made the genome-edited bull a GMO, because it contained foreign DNA from another species, in this case a bacterial plasmid.

“We’ve demonstrated that healthy hornless calves with only the intended edit can be produced, and we provided data to help inform the process for evaluating genome-edited animals,” said Van Eenennaam.

“Our data indicates the need to screen for plasmid integration when they’re used in the editing process.”


Hornless cattle make case for gene editing and less restrictive regulation of GM animals

Hornless cattle, described by GLP’s Jon Entine here last year, have lumbered onto the GMO scene once more. This time they appear as an example in Antonio Regalado’s speculations at Technology Review about the future of GMO regulation, especially animal biotechnology.

Because the cattle are made using gene editing techniques and no genes from other species, the hope by some is that regulators will accept them more readily than they have GM animals produced in other ways. The hornless cattle are the brainchild of molecular geneticist Scott Fahrenkrug, who used to be at the University of Minnesota but left to form his animal GMO startup, Recombinetics. He wants to breed GM pigs as model animals for human disease research as well as cattle without horns.

Hornless cattle are desirable because they are less dangerous to people and to each other. Some breeds are hornless naturally, but dairy cattle breeds usually have horns that are burned or sliced off, a horribly painful process. A Recombinetics investor who took part in dehorning in his youth told Regalado that it was a bloody mess. “You wouldn’t want to show that on TV.”

Fahrenkrug, whose company is using a gene editing method called TALENs, is not the only scientist hoping that gene editing will pass muster with regulators. A few weeks ago I wrote here at GLP about a gene deletion, using a different gene editing technique called CRISPR, which helps wheat resist powdery mildew. The hope is that because the work did not involve gene transfer it will not arouse opposition.

Is gene editing close enough for government work?

It’s not clear that organisms made via gene editing techniques will be able to avoid the name-calling and regulatory suspicion usually heaped on GMOs. Optimists are hoping that gene-edited products will impress regulators when they contain no foreign genes and so make it to market.

The Chinese scientists who developed the disease-resistant wheat said that explicitly. China has invested in research on GM crops but has approved none for field-testing recently, ostensibly in response to public concern. Two plant geneticists (one from China) took to the pages of PLOS Biology in June to make the case for regulatory approval of genetic modification of plants that does not involve “foreign” genes. In addition to gene editing methods like CRISPR, there are plant GM methods that resemble natural mutations, and also mutations produced by techniques long accepted in agriculture, such as those induced by chemicals, X-ray, and gamma rays.

The hornless cow people are hoping for regulatory benignity too. A hornless cow has a uniquely attractive quality: its purpose is to produce dairy herds that don’t have to undergo the painful de-horning procedure now common in the industry. This is a GMO that is the embodiment of kindess to animals, in contrast to the complaints often leveled against genetically engineered livestock. Good PR for a change?

The question of “foreign” genes is a little iffier here though. Hornlessness is produced by insertion of genes from other cattle breeds that are naturally hornless. “We’re talking about genes that already exist in a species we already eat,” Fahrenkrug told Tech Review.

Is that close enough for government work? Would the Food and Drug Administration nod and approve its first genetically modified food animal because–although a hornless dairy cow is, strictly speaking, a transgenic organism–it contains only inserted genes from the same species?

Even if the argument is persuasive with regulators, would it fly with the general public, and particularly with opponents of genetic modification? I’m doubtful. For one thing, the professional GMO antagonists often have agendas not directly related to genetic modification, for example opposition to agricultural multinationals. For them, how GM is done doesn’t matter much.

For others, a lot of the unease with genetic modification appears to involve inchoate worries about “tinkering with Nature” and “playing God.” For people with those concerns, the methods of genetic modification are irrelevant. It’s the very idea of genetic modification that worries them.

Note also that not all applications of gene editing are transgene-free. Presumably they would encounter the same objections made to any GM project involving insertion of foreign genes. One extraordinary example: The breathtaking proposal to modify the genes of the entire species of mosquito that carries malaria. The proposal employs CRISPR gene editing. But it also involves insertion of a gene, designed by the researchers, that would make mosquitoes resist the malaria parasite. My July GLP article about this plan, and proposals made by the researchers themselves for public discussion of this massive project, is here.

Bringing home CRISPR bacon

Meantime, gene editing, especially CRISPR, continues to take genetic science by storm. (Here’s my GLP description of how CRISPR works.)

In just a year, Spanish researchers say, CRISPR has made possible “an immense range of genetic modifications in most model organisms.” With CRISPR, multiple genetic modifications can be introduced seamlessly in a single step. It has enabled precise genetic engineering of organisms with difficult-to-edit genomes. Also technically challenging species. (They are speaking here of primates.)

Scientists at the Université Laval in Quebec report that they have used CRISPR to alter virulent phages. Phages are viruses that infect bacteria, not people they can’t even recognize animal cells. That kind of thing will make it possible to study relationships between phages and their hosts, and presumably could lead to engineered phages that could destroy disease bacteria.

CRISPR and other synthetic biology techniques will lead to cures for diseases of neurodegeneration, according to researchers at Imperial College London.

On September 5 in Science, scientists at the University of Texas Southwestern Medical Center announced that they had prevented muscular dystrophy in mice by using CRISPR to correct the mutation that causes it. They did this in the mouse germline, so the correction showed up in their offspring. The plan for humans is to cure the disease, not prevent it, by correcting disease-causing mutations in the muscle tissue of patients with muscular dystrophy.

But why wait until a patient has suffered? Why not prevent the disease long before birth? Researchers at the University of Wisconsin say the CRISPR “system is poised to transform developmental biology by providing a simple, efficient method to precisely manipulate the genome of virtually any developing organism.”

Franco J. DeMayo and Thomas E. Spencer, Editors-in-Chief of the journal Biology of Reproduction, declared last month that CRISPR “is completely revolutionizing genome engineering.” This was a commentary on “sizzling work” describing the “easy and efficient” way CRISPR generates genetically engineered pigs. They say the techniques are critical to developing new animal biomedical research models, agricultural animals with specific desired traits achieved without a complicated breeding scheme, and therapeutics to correct human and animal diseases. “In summary, we expect this technology to revolutionize all aspects of science.”

Wow. That’s a pretty comprehensive forecast. And please believe me when I tell you that these examples are just a few highlights. There’s more, much more about the coming glory days of gene editing methods, especially CRISPR. My point is to emphasize once more the unprecedented power that scientists are claiming for these techniques. And it’s not just boyish enthusiasm and hype. They think gene editing, which employs a tactic that bacteria invented 3 billion years ago for warding off disease, is light-years better than other genetic engineering techniques. Easier. Cheaper. And therefore bound to become more widespread.

And just to be clear, we are not talking here only about plant and animal GMOs. In a New England Journal of Medicine paper recounting gene editing techniques for modifying primate embryos and calling for public discussion of the implications of this work, scientists at the University Medical Center Freiburg, Germany said this: “The successful genetic editing of one-cell primate embryos raises ethical issues that go beyond the balance between the scientific value of transgenic monkey models in understanding human disease and concerns about their creation. These studies bring us one step closer to the potential for manipulating genes in human embryos.”

Tabitha M. Powledge is a long-time science journalist and a contributing columnist for the Genetic Literacy Project. She also writes On Science Blogs for the PLOS Blogs Network. Follow her @tamfecit.