Many scientists and animal breeders are keenly interested in directly altering a portion of an organism’s genome to incorporate specific traits. For example, the company Recombinetics recently created two bulls by altering their genome to introduce the polled gene. We know that we already can selectively breed for polled animals by identifying sires or cows that carry the dominant polled gene. What was different about the Recombinetics bulls is that those animals were clones of a horned bull.The intention all along was to create clones that were genetically identical to the original horned bull except for the polled gene. That effort was mostly successful, and the two homozygous polled clones were moved to the University of California-Davis for further evaluation. One of those bulls was subsequently mated to horned cows and the resulting offspring were all polled, indicating that the polled gene was successfully incorporated into the genome of what was once a horned bull.
A faster future
The ability to make what is now known as intentional genomic alterations — or IGA — could speed many genetic selection efforts. For the most part, gene editing won’t help with traits such as milk yield, but there are many other possibilities. The top genetic lines could quickly be altered to be:
- Homozygous polled
- A2 beta casein genotype
- Free of all genetic recessives
- Slick hair-coat gene inserted for heat tolerance
- The best version of genes for cheese yield
We are currently working to do many of these through sire selection, but it will take many years using the current system. In theory, gene editing could get it all done in a generation. You can see why many are intrigued by the prospects.
The technologies to create gene-edited organisms rely on bacterial genes and systems. The best known of these systems is CRISPR/Cas9, although the polled bulls were created with a system known as TALENs. Regardless of the gene-editing system, specific DNA sequences are targeted and the genome is altered by changing the DNA sequence, adding genetic material, or removing genetic material. Generally, the systems are designed to make changes in very specific regions of the genome.
In the case of the polled gene, scientists were replicating a natural mutation that occurs in cattle. There is also the possibility of introducing new or novel mutations. This was done for the creation pigs that are resistant to Porcine Reproductive and Respiratory Syndrome, or PRRS.
The PRRS virus had a devastating effect on the U.S. hog industry, causing pregnant sows to abort their litters and causing death in young animals. Scientists studied how the PRRS virus attacked cells and noticed that they used a very specific protein expressed on the surface of cells in pigs. They employed gene editing to remove a portion of the gene that codes for that protein. As a result, the pigs were resistant to the PRRS virus and created a lot of excitement about the possibilities of using gene editing in livestock.
Most scientists believe that gene-edited cattle and pigs are perfectly safe for human consumption. If you’ve ever eaten beef from an Angus, you’ve consumed meat from animals that carry the exact same mutation that was thought to be introduced through the gene editing process for the polled condition — the polled gene in Holsteins is a slightly different mutation in the same region of the genome.
Such technologies are regulated by various government agencies, and the regulations vary from one country to the next. Governments in South American countries such as Brazil were generally inclined toward permissive use of such technologies. That’s provided that companies were not introducing genes from one species into another, which would be considered a genetically modified organism or GMO.
The U.S. perspective
Our Food and Drug Agency (FDA) has taken a more restrictive stance. They have made it clear that IGA will be regulated much the same as the introduction of new antibiotics and drugs. The regulatory process required to gain approval of a new drug is very long and very expensive. FDA’s position was heavily criticized by many scientists and companies involved with gene editing.
Scientists involved with the gene-edited polled bulls decided to test their luck a bit with the FDA. They alerted FDA regulators that they would like to send the animals to slaughter since they were largely done with the research project.
The good news is that the request did cause FDA to speed up its evaluation of the gene-edited bulls. The FDA scientists evaluated the genome sequence of the bulls and reported that alterations were in fact made at the intended site.
The bad news?
While alterations occurred where they were supposed to, the type of alterations were not entirely what was hoped for. In addition to the polled mutation, they found bacterial DNA in the bulls’ genomes. Scientists involved with the project had examined the genomes to make sure the polled mutation was incorporated properly but had overlooked the possibility that a bacterial gene could accidentally be introduced at the same time.
That sounds like a serious oversight, but those involved with genome sequencing are probably not surprised. Combing through an animal’s DNA sequence is not a trivial task — there are around 6 billion DNA base pairs inherited from our parents, and we aren’t able to read a genome from front to back the way we can read a book.
The FDA scientists screened more directly for the bacterial genes. They also found evidence that in one of the bulls, multiple copies of the polled mutation were introduced rather than just one.
The presence of the bacterial DNA immediately changed the status of such animals from IGA to GMO. That change will mean more regulations in the U.S. and in those countries that previously had more relaxed regulations.
GMOs are common when it comes to plants but rare when it comes to animals. The lone GMO animal product is salmon produced by a company named AquaBounty. It took AquaBounty approximately three decades to get approval for its product to be sold in the U.S.
A look to the future
Scientists have different reactions to these latest developments. Some have pointed out that the bulls were produced with an older technology and that newer technologies are less susceptible to inadvertent modifications. Even if there are such changes, the food produced is still safe.
Others will point out that gene editing is still a relatively new technology and that we have a lot to learn. Some have been warning that there are more inadvertent changes than appreciated and feel that this latest development validates those concerns.
The field of gene editing is advancing rapidly, but this latest development is likely to set efforts back to some degree. So, for those who want polled cattle, A2 milk, and the slick hair coat, it looks like you will need to utilize good old-fashioned sire and dam selection. That process has worked quite well for a long time and will continue to do so until gene editing becomes an approved part of our genetic improvement toolbox.