Gene-Editing, Is it a Reality?

GENE EDITING – IS IT A REALITY?

by Darrell Wilkes, Ph.D., International Brangus Breeders Association (IBBA) executive vice president

The term “gene editing” has been kicked around for several years and may have created more confusion than enlightenment. The thought of it might also create some anxiety among seedstock breeders who fear that their many years of selection and traditional genetic improvement could be leap-frogged by some mad scientist in a lab. I have had conversations with breeders who fear that such technology will result in a complete restructuring of the seedstock industry such that large biotech companies will “take over” the seedstock business. The fear is that the biotech giants will hold patents on certain genes or gene combinations and everybody else will be reduced to multiplying their genetics under a license agreement. Simply put, such fears are unfounded.

If one considers the broad spectrum of what is generally called “genetic engineering” and create a scale of one to ten with one being the most simple and basic applications and ten being the most extreme (almost science-fiction like) applications, gene editing would be scored a 1. Gene editing, as used in reference to cattle, will not create any genetic characteristics that could not otherwise be created through normal breeding strategies.

An example may help explain the simple nature of gene editing.

As most cattle breeders now know, DNA is made up of nucleotides. There are only four them in DNA. They are Adenine, Thymine, Guanine and Cytosine – and are abbreviated with the first letter of each – A T G C. The sequence of these letters provides the instructions for making a specific protein. A gene is nothing more than a string of these letters.

For the sake of simplicity, let’s assume the following sequence of nucleotides codes for black hair color:

A A T T C C G G. Let’s assume that the gene for red hair color is A T A T C C G G. The only difference is that the second and third letters are switched. One application of gene editing is to simply cut the DNA strand with special chemical scissors and literally switch the order of the letters. This is truly an edit. It is not unlike editing a misspelled wrod (word). In this simple example, it does not involve inserting a gene from a different breed or even a different animal from the same breed. It simply rearranges the nucleotides that are already there and it creates a gene variant (allele) that already exists – in this illustration, a gene for red hair.

Does this mean that you can create a Red Brangus from a Black Brangus, for example? Yes, that can be done.

The rest of the story is what I have discovered is confusing to people. How does this “microsurgery” of DNA change the color of an animal? It does not change the color of the source animal. The process requires that a new animal be created with the edited DNA. There are a couple of ways to do this, but a common one is through cloning, which is already a proven and commercially available technology. You take a regular body cell (a somatic cell) from the animal that you want to clone. Next, you edit the DNA similar to the example above. You then put the edited cell into an egg where the nucleus of the egg has been removed - stated more clearly, the DNA that was in the egg is taken out and the edited somatic cell is inserted. The egg now becomes an embryo. Nine months later, a calf is born. It will be genetically identical to the source animal with the exception of the hair color gene. If the source animal was black, and the red edit was performed, then the new animal will be red and will breed like any naturally-occurring red animal.

Some breeders have already created a red clone of a black Angus bull. The calf is too young to be a parent, but it will soon be old enough to produce semen and the breeders will surely mate that animal to some red Angus cows to see if it really works. There is absolutely no reason to think it will not work since the edited gene is identical to the naturally occurring red gene in red cattle.

Gene editing was discussed in several seminars during the 2021 Beef Improvement Federation conference in Des Moines. One of the traits frequently mentioned in connection with gene editing was heat tolerance. It should come as no surprise that every breed that does not have a dose of Bos indicus genetics would like to be able to edit a couple genes and create cattle that match the heat tolerance of Brangus without dealing with the indicus influence. One gene in particular is called the “slick” gene and creates a slick and sleek hair coat that helps animals regulate internal body temperature in hot/harsh environments. The “slick” allele occurs naturally in Senepol cattle. USDA researchers in Florida showed that animals with the “slick” gene and the corresponding sleek hair coat were able to maintain a body temperature 1-degree Fahrenheit lower than cattle without the gene.

Before Brangus breeders get too worried about a single gene edit having the ability to make Angus, for instance, as heat tolerant as Brangus, it must be pointed out that virtually every complex trait is affected by dozens if not hundreds of small gene effects. Heat tolerance or, more accurately, thermoregulation, is certainly a complex trait. Editing one or two genes in Angus is very unlikely to impart the same level of thermoregulation ability that Brangus cattle naturally possess. Still, it is important for Brangus breeders to understand that heat tolerance (thermoregulation) is seen as a potentially highly rewarding target for gene editing research. You can expect to read and hear much more about this in the years ahead.

Gene editing is not without some challenges from a regulatory standpoint. If edited animals or their progeny are prevented from entering the food chain, the technology will die a sudden death. Currently, the Food and Drug Administration (FDA) has regulatory authority over the food products produced from “genetically engineered” animals. Even in those cases where the edit is very simple and straightforward, not to mention naturally-occurring, such as the black-to-red edit, FDA will ultimately decide if such edited animals (and/or their progeny) are safe to enter the food supply. At present, FDA is evaluating this on a case-bycase basis.

A final point of interest on gene editing involves breed association policy. Obviously, in the beef industry, the animals most likely to be edited are animals that already have a comprehensive genetic evaluation and are believed to have very high genetic value for the traits included in the evaluation. These are registered animals. Hence, breed associations will be faced with a decision on how to handle gene-edited animals. Can they be registered? If so, how should they be “earmarked” as either an original edit or the progeny of an edited animal. IBBA’s Breed Improvement Committee will be addressing this issue in the coming months.