Taking genes to the next level

And he can. Because of a new “gene-editing” technology called CRISPR, the University of Adelaide geneticist could now do this gene trade quickly and relatively simply.

Had he attempted the same process using the traditional route of genetic modification, it might take years, the process would be imprecise, and the results would be uncertain.

But if old-school genetic modification is a bit like trying to do surgery with a shovel, gene-editing using CRISPR is surgery with tweezers and scalpel. It should be: it’s not a human invention, but the discovery of a DNA-level process that bacteria use to protect themselves against viruses. (See https://www.quantamagazine.org/20150206-crispr-dna-editor-bacteria/)

For scientists like Dr Williams, CRISPR is an incredible research tool.

Texel double-muscling might be bred into Merinos, but it would take generations. Meanwhile, genetic progress in other areas, like wool production, would likely slip behind in the quest for muscling.

Traditional genetic modification might do it, but it would be a lengthy, prohibitively costly process that in the end, might produce a sheep shunned by GM-adverse consumers.

The new gene-editing technologies eliminate the issues with time and imprecision (and much of the cost) and cut straight to the heart of the matter: what happens when bits of a genome are cut-and-pasted from one type of animal to another?

To make a poll from a horned livestock breed, it might be really as simple as cut-and-paste, Dr Williams said.

But genes never work in isolation. They interact in complex ways, like the balls on a pool table when the white ball is cannoned into them. So when one gene is altered, the lights will be blinking on and off in other areas of the genome in unpredictable ways.

That’s why Dr Williams has applied to the Australian Research Council for funding to do his Texel-Merino double-muscling experiment. He thinks it highly likely that the Merino with the Texel muscling mutation would be more highly muscled than a standard Merino, but he doesn’t know what other effects the transplant will produce.

“If the gene-edited Merino sheep are eating the same amount of food, do they then repartition that energy away from the wool production to give extra muscling?”

“Or do they maintain wool production? Or is there an impact on organ development or bone development that may affect survival?”

During nearly a decade at the University of Edinburgh’s Roslin Institute - famous for producing Dolly the cloned sheep - Dr Williams contributed to research looking at the myostatin mutation that gives Belgian Blue cattle their distinctive body-builder look.

That mutation is in Angus and South Devon cattle, Dr Williams said, but when the same allele in the same homozygous state that causes the extreme look in Belgian Blues is present in South Devon, the Devon express double muscling to a much less degree.

“So the genome editing is at this stage where, yes, we can move an allele from animal to another very rapidly. What the phenotypic effects will be, and what the gene interactions will be, we can’t yet predict.”

What the public make of gene-editing also remains to be seen.

Scientists hope to portray to process in a very different light to the maligned GMO process, but CRIPR’s image wasn’t helped by publicity around Chinese experiments to replace genes for blood disorders in “non-viable” human embryos. That quickly led to speculation about the prospect of “designer babies”.

Dr Williams is pragmatic.

“In the Merino project, we’re saying this is proof-of-principle. We can quickly make a gene-edited sheep and see what the effect is. If the public is not happy with this sort of molecular intereference, we can say to the breeders, ‘If you were to do this selection that might take you 5-10 years to complete, we can tell you tomorrow what the effect will be.”

“You can quantify whether this is advantageous from the perspective of natural breeding. Breeding is going to take a long time, but at least we know the result of bringing that allele into the breed before we start.”

If Dr Williams Texel-Merino CRISPR project is funded, he anticipates it will be about three years before results are reported.