Section 1.1: The Birth of a Gene-Edited Calf

On a bright Tuesday in April during the global pandemic, a newborn calf took its first tentative steps in a barn near Sacramento. Researchers Alison Van Eenennaam and Joey Owen watched in amazement as this wasn’t just any calf; it was a gene-edited bull named Cosmo, engineered to produce a higher number of male offspring.

The creation of Cosmo was the culmination of five years of intensive research. Nine months prior, Van Eenennaam, Owen, and their team employed the CRISPR gene-editing tool to insert the SRY gene into cow embryos, including the one that developed into Cosmo. This gene is crucial for male sexual development in cattle, and introducing it to a female embryo effectively alters its sex. The researchers aimed to create a bull that would sire primarily male calves.

“The initial concept came from a cattle rancher,” explains Van Eenennaam, PhD, affiliated with the University of California, Davis.

Male cattle are preferred in beef production due to their larger muscle mass, faster weight gain, and lower feed requirements compared to females. According to Van Eenennaam, bulls are roughly 15% more efficient in converting feed into weight. Therefore, increasing the male calf population could lead to fewer cattle needed for the same meat output, benefiting both ranchers and the environment.

To achieve this, the team injected around 200 cow embryos with CRISPR and the SRY gene, also incorporating a green fluorescent protein used in biomedical research to indicate successful edits. Ultimately, approximately two dozen embryos survived, with only nine showing the desired fluorescence.

CRISPR technology works by creating a precise break in DNA with a guide molecule that locates the target area and a cutting protein that cleaves the specific genetic sequence. Although deleting genes with CRISPR is straightforward, inserting new genes presents a greater challenge.

The nine successfully edited embryos were then implanted into female cows. Out of these, only one cow became pregnant. Following a nine-month gestation period, Cosmo was born a week later than expected, on April 7, amidst the California lockdown due to COVID-19.

“That was a nerve-wracking week,” recalls Van Eenennaam. The announcement of Cosmo's birth was made on July 23 during a virtual gathering of the American Society of Animal Science, though the findings have not yet been peer-reviewed.

Section 1.2: Expectations vs. Reality

Similar to humans, cows have an equal chance of birthing male (XY) or female (XX) calves. However, Cosmo is projected to produce a higher proportion of male offspring. The anticipated breakdown includes 50% XY males and 25% XX females, which will also possess the SRY gene, potentially resulting in male reproductive characteristics and muscle mass. Thus, approximately 75% of his progeny are expected to exhibit male traits.

Researchers are still uncertain whether Cosmo will indeed yield more male calves than non-edited cows, as he will not reach sexual maturity for another year. Only then can he be bred, providing answers to the team's hypotheses.

Jon Oatley, PhD, who leads the Center for Reproductive Biology at Washington State University, warns that current findings are preliminary. He notes that even if Cosmo’s XX offspring inherit the SRY gene, they may not resemble typical bulls. This genetic makeup could be akin to Klinefelter syndrome in humans, leading to developmental irregularities, including diminished muscle development.

Oatley expresses concern regarding the use of the green fluorescent protein, typically reserved for laboratory animals, emphasizing that it is not intended for animals raised for food. Van Eenennaam states that should she pursue regulatory approval for these bulls, the fluorescent protein would be eliminated.

Moreover, researchers uncovered an unexpected detail in Cosmo's DNA after his birth. A blood sample revealed not just one, but seven copies of the SRY gene were successfully inserted. While Cosmo appears healthy, the presence of multiple gene copies indicates that CRISPR can yield unforeseen results in the genome.

An additional unanticipated finding was the integration of bacterial DNA used to facilitate the CRISPR process into Cosmo's genetic material. A similar issue occurred previously with hornless dairy cattle developed by Van Eenennaam and her colleagues at UC Davis in partnership with Recombinetics.

Section 1.3: Previous Gene-Editing Efforts

To create hornless cows, scientists employed an earlier gene-editing technique known as TALENS. Reports from last year confirmed that these gene-edited bulls successfully passed on the hornless trait to their offspring. Many cattle breeds naturally grow horns, but their removal is common practice to prevent harm, although this method is often criticized for being painful.

In China, researchers have also used CRISPR to develop cattle resistant to bovine tuberculosis, a highly contagious disease that can be costly for farmers, as infected animals must be culled to prevent further spread.

At present, the gene-edited cattle produced by Van Eenennaam’s team are designated for research purposes and will not enter the food supply. The U.S. Food and Drug Administration treats gene-edited animals as drugs, resulting in a lengthy and complex approval process. As of now, no gene-edited food animals are available in the U.S. marketplace.

Meanwhile, other significant beef-producing nations like Argentina and Brazil appear more receptive to gene-edited livestock. However, Brazil's plans to introduce gene-edited cattle were suspended last year due to concerns over the presence of bacterial DNA found in Recombinetics' livestock. In China, scientists are also gene-editing pigs to combat African swine fever, which has heavily impacted the nation’s pork supply. Van Eenennaam suggests that the U.S. is likely years away from having gene-edited cattle or pigs available for commercial sale. "I don’t expect that we will see them in America anytime soon."