A few years ago, a Minnesota-based company called Recombinetics had done something revolutionary, or so they thought. They gene-edited Holstein bulls to be hornless. Sounds impressive right? I mean, normally the horns have to be surgically removed (a very painful procedure) so this would appear to be a monumental achievement. It would have been the launch of a gene-editing revolution for sure… if it wasn’t for a mess up in the process which involved rogue DNA from bacteria inserting itself into the animal’s genome and going almost undetected!
When the US Food and Drug Administration (FDA) conducted an investigation into the safety of the modified bull’s DNA, they found the genome to be contaminated by bacterial DNA, some of which has been linked to antibiotic resistance. As a result, Recombinetics is having to drop its plans to breed horn-free cattle.
In a subsequent report, the FDA officials concluded: “Our discovery highlights a potential blind spot in standard genome editing screening methods.” It goes on to recommend modifications for current screening methods, which would “enable better detection of undesirable genetic additions such as these.”
This whole ordeal was a massive disappointment to Recombinetics as they believed their hornless cattle were “messengers of a new era” of better, faster, molecular farming. “This same outcome could be achieved by breeding in the farmyard,” declared the company’s then-CEO Tammy Lee Stanoch in 2017. “This is precision breeding.” The blooper that occurred during the gene-editing process went completely undetected by the company who touted the animals as 100% bovine and assailed the FDA for saying the animals needed to be regulated at all.
Tad Sontesgard, CEO of Acceligen, a subsidiary of Recombinetics that owns the animals said:
It was not something expected, and we didn’t look for it. A more complete check should have been done.
So how exactly did this happen and how did they manage to make the bulls hornless, regardless of the bacteria DNA mistake?
- First, the company’s scientists started with skin cells from Holstein dairy bulls.
- Then, plasmids (circular genetic structures found in bacteria) were used to carry DNA instructions called TALENs (transcription activator-like effector nucleases) to these skin cells. TALENs are enzymes that can be modified to cut out sections of genetic code. The cut out sections can then be filled with DNA from other species – in this case, DNA related to hornlessness acquired from a horn-free cattle breed.
- The plasmids were only meant to persist temporarily. They were supposed to carry the DNA instructions for the TALEN and then plug the “no horns” genes in and move on. In this case, however, they stuck around and stuck themselves in next to the DNA for hornlessness.
The company had been paving the way as far as genetically-modified animals go until this point. Spotigy and Buri, their two hornless Holsteins unveiled in 2015, had been seen as “poster animals for the gene-editing revolution”. Buri had gone on to father 17 calves and bottles of his sperm were about to be shipped off to Brazil to conceive more hornless Holsteins. Of course, they discarded it all. Meanwhile, other animals are in the process of being created, including castration-free pigs and heat-resistant cows.
