Part cow, part … bacteria? A biotechnology company creates a heifer goose for gene editing

A Minnesota-based gene editing company has a red face after adopting bull genetics and has been criticized.

The Recombinetics company decided several years ago that genetic engineers of Holstein dairy cattle, without their awkward horns, that farmers usually remove to ensure their safety and that of other cows. In 2015, the company seemed to have succeeded, unveiling two hornless bulls, Spotigy and Buri. Recombinetics has touted them as a true 100% bovine success story.

Although Spotigy was sacrificed for research purposes, Buri survived to spawn 17 children, one of whom wore the cover of Wired, as noted in the journal MIT Technology Review. And, just a few months ago, Brazil was about to create a herd of Hornless Holstein from Buri's sperm shipments, Wired reported.

But the plans were overthrown after scientists at the Food and Drug Administration came across an absolutely overwhelming discovery early in the year: Buri is not a bull, he is a tiny bacteria.

Bullish changes

When Recombinetics published the cow cells that would give birth to Buri, the company did it with the help of a bacterial DNA editing device, which was inadvertently sewn into the Buri genome.

The implicated machines are called TALEN (transcription activator-type effector nucleases), which are enzymes that can be customized to cut a targeted spot into a genetic code. This break in the code can then be corrected with a desired DNA sequence, for example a portion of the DNA that leads to the absence of horn, extracted from other cattle breeds without horn.

Recombinetics scientists used a standard method to introduce TALENs into cow cells: they delivered the TALENs via a loop of bacterial DNA called plasmid. Usually, once the plasmid-encoded TALENs have cut them, the plasmid work is complete and does not drag. But in the case of Buri, the entire plasmid eventually inserted into the bull's genome, right next to the inserted DNA segment to ensure the absence of horn.

This means that the Buri genome contains all of the plasmid DNA sequence. And in addition to all the bacterial editing machinery of the DNA loop, the Buri genome includes the antibiotic resistance genes present on the plasmid – even if they are not likely to. 39, to have effect.

Blind spot

The insertion of the plasmid is a large cow plant. But the fact that society has not found the problem itself is perhaps more embarrassing.

"This was not planned and we did not look for it," said MIT Technology Review's Tad Sonstegard, CEO of Acceligen, a subsidiary of Recombinetics that owns the animals. He added that a more thorough audit "should have been done".

FDA scientists who found the problem accepted. In their report on the case, they noted that their discovery "highlights a potential blind spot in standard screening methods for genome editing".

Although embarrassing, genetic insertion is unlikely to affect cows or those who might eat them. As Sonstegard says, they are "sure to eat with or without the plasmid".

But the inclusion of bacterial DNA in the genome of a cow makes the regulatory aspects of Buri and its offspring much more complicated, virtually unsustainable. They are not just cows to cow, they are edited, they are genetically modified organisms with DNA from a branch of life completely different.

Some of the animals have already been cremated and the Brazilian control authorities have rejected plans for them.

Recombination, meanwhile, does not ruminate on the blunder. He has already made progress with heat-modified and heat-tolerant beef. The company noted that it had found no bacterial genes in these animals.