Genome editing results in animal welfare breakthrough

By Joan Conrow

October 7, 2019

In a major animal welfare breakthrough, a new study published in Nature Biotechnology confirms that a genome-edited bull can successfully pass on the hornless trait to his calves.

The paper also demonstrates that publicly funded university researchers and federal regulators can effectively work together to ensure that only correctly developed animals would be taken forward into breeding programs.

University of California, Davis researchers have been collaborating on this project, which seeks to eliminate the need for the unpleasant process of removing horns at an early age to ensure the safety of other cows and dairy workers. The first hornless bull calves were produced by Minnesota-based company Recombinetics and were born in April 2015. One of the bulls was bred with horned cows at UC Davis to investigate whether the polled allele would be faithfully passed on to offspring. This resulted in the birth of six healthy “polled” (hornless) calves.

“Genome editing offers a pain-free genetic alternative to removing horns by introducing a naturally-occurring genetic variant, or allele, that is present in some breeds of beef cattle such as Angus,” said corresponding author Alison Van Eenennaam of the Department of Animal Science at UC Davis.

However, activists opposed to biotechnology misrepresented and sensationalized the results of the study before it could be published. They launched a social media blitz this past July that made references to “bacterial contamination” and “major screwup.”

“Such work takes time and should be accurately represented and placed in context, not irresponsibly reported in sensational scare pieces,” Van Eenennaam said.

In fact, the analysis conducted by the US Food and Drug Administration — using data generated and supplied by the researchers — found that a fragment of bacterial DNA, used to deliver the hornless trait to the bull, had integrated alongside one of the two hornless genetic variants, or alleles, that were generated by genome editing in the bull. UC Davis researchers further validated this finding.

“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,” Van Eenennaam said.

Plasmid does not harm the animals; indeed, such sequences are present in the trillions of bacteria that inhabit our microbiome. 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 never had offspring of genome-edited cattle to research before, so our job as public scientists working with the FDA is to look for the unexpected,” Van Eenennaam said. “We found the plasmid segregating in the offspring, which indicates the need to screen for plasmid integration when they’re used in the editing process.”

Scientists did not observe any other unintended genomic alterations in the calves and all animals remained healthy during the study period. Neither the bull, nor the calves, entered the food supply as per FDA guidance for genome-edited livestock.

None of this information was presented by activists, who also failed to note that this was a research project, conducted precisely to gather more data about a new process in breeding livestock. Going forward, plasmid introgression can be readily addressed by screening and selecting only those with the intended edit, like the two offspring that did not inherit the allele. Furthermore, new methods have been developed that no longer use plasmid or other extraneous DNA sequence to bring about introgression of the polled allele.

Unfortunately, Van Eenennaam said, “this type of irresponsible fear-mongering” muddies the public discussion around genome editing in livestock and potentially results in this technology facing a more challenging path through the regulatory process, thereby delaying the introduction of beneficial disease-resistance and animal welfare traits.