Thanks to a peculiar mix-up involving Holstein bulls, CRISPR, and rogue DNA (from bacteria, no less), a Minnesota-based company called Recombinetics is having to scrap plans to breed horn-free cattle.
An investigation led by the US Food and Drug Administration (FDA) found the genome of a gene-edited bull contained bacterial DNA, some of which has been linked to antibiotic resistance. In a subsequent report, published in July, officials concluded: "Our discovery highlights a potential blind spot in standard genome editing screening methods."
Going forward, the watchdog recommends modifications to current screening methods, which would enable better detection of undesirable genetic additions such as these.
This result comes as a major blow to a company who until quite recently, appeared to be paving the way as far as genetically-modified animals are concerned. When their two hornless Holsteins, Spotigy and Buri, were unveiled in 2015, they were seen as "poster animals for the gene-editing revolution," MIT Technology Review reports.
The purpose of these edits was to breed Holstein cattle that do not grow horns, which – in unedited cattle – have to be removed. A process the American Veterinary Medica Association says "is considered to be quite painful".
Spotigy had to be sacrificed for research but Buri went on to father 17 calves. Meanwhile, bottles of his sperm were due to be sent to Brazil to conceive more hornless Holsteins, but have now been scrapped. Other animals in the pipeline included castration-free pigs and heat-resistant cows.
So, what happened? To put it simply, there was a mix-up in the editing process.
Plasmids (circular genetic structures found in bacteria) were used to carry DNA instructions – or TALENs (transcription activator-like effector nucleases) – to samples of skin cells extracted from Holstein cattle. TALENs are enzymes that can be modified to cut out sections of the genetic code, which can then be filled with DNA from other species – in this case, DNA related to hornlessness acquired from a horn-free cattle breed.
If all goes to plan, the plasmids are only temporary. However, in this example, it stuck around and inserted itself into the genetic code alongside the DNA for hornlessness.
The error (and the fact that it went on undiagnosed) is an embarrassing blunder for a company that has been so vocal in its opposition to FDA oversight in regards to gene-edited animals. One that has even campaigned to have the responsibility of oversight taken away from the agency.
But, as the MIT Technology Review reports, this doesn't just pertain to livestock. Errors like these could very well apply to potential medications and treatments to cure diseases in humans – or even, in rarer instances, the genetic editing of human embryos (like the CRISPR twins earlier this year) that scientists are worried could lead to unintended genetic mutations.