Surrogate sires may boost production

As an example of how the technology might work, breeding males of the hardy Nelore cattle of South America could be sterilized using the CRISPR tool and used as surrogates receiving sperm-producing stem cells from Angus donors. | Reuters/David Mercado photo

According to the United Nations’ Department of Economic and Social Affairs, the world’s population is expected to reach about 9.7 billion by 2050.

Jon Oatley, director of the Center for Reproductive Biology at Washington State University, has been working in the molecular biosciences field for 20 years researching strategies to provide nutritional requirements for this population boom. He estimates it will require a 60 percent increase in agricultural efficiencies to feed 10 billion people at today’s nutritional requirements with the same amount of food and animal protein.

“To make this even harder, we’re asking animals to be more resilient with dwindling water supplies, poorer quality feeds and in variable climates. I believe we need to make larger and faster gains in genetic improvement than we ever have. And animal protein must be a major source for the human diet.”

While North America and parts of Europe and Asia are breeding superior beef and dairy cattle, underdeveloped countries lag far behind.

Genetic advancements normally occur through natural breeding requiring several generations, or through artificial insemination, offering quicker results but also increased logistical challenges in many areas of the global agricultural community.

To counteract this problem, Oatley’s department at WSU has helped develop the concept of “super daddies.”

“The whole premise is to deliver a new strategy of large scale and widespread dissemination of elite or desirable genetics in a range of livestock production settings including swine, cattle, sheep and goats.”

He says at its core, adapted native males are first engineered to be sterile, then receive sperm-producing stem cells from an elite donor. Batteries of resulting males producing sperm and carrying these superior genetics could be used in natural-mating schemes. They would provide genetic gain and alter traits for production efficiency and resiliency.

Oatley describes the process to create these surrogate sires as two parted.

First, hardy males able to thrive in a local climate and environment are made sterile. They would have normal testicular tissue, physiology and biology but lack the cells needed to produce sperm.

“The testicles are essentially open, empty vessels by which to introduce new sperm producing cells,” he says.

Second, sperm-producing stem cells are transferred from a desired male to the sterile surrogate allowing them to begin producing the sperm containing the genetics of the elite animal.

Sterilization of host males, harvesting of stem cells and their transfer to surrogates had been problematic in the past for health reasons but advances in technology have ensured animal safety and negated environmental impacts.

Instead of using chemotherapeutic drugs, which were never completely successful and caused health issues and biohazardous waste, the process of sterilization now begins with CRISPR Cas9 technology — a molecular tool to create small changes in DNA sequences and modify gene function.

The NANOS2 gene was identified in mouse trials to be inactivated for sterilization but it wasn’t known if it would react in the same way with other larger animals.

“We used CRISPR to knock out this gene in pigs, cattle and goats and similar to what we discovered in mice, the only impact on the biology was they became sterile.”

The subsequent question was how the transfer of sperm-producing stem cells would work.

“We showed in all those species it worked well. We could take sperm-producing stem cells from our desirable donor, transfer them into a CRISPR sterile male, and he would create the sperm of the donor.”

As an example of how practical deployment might work, breeding males of the hardy Nelore cattle of South America could be sterilized using the CRISPR tool and used as surrogates receiving sperm-producing stem cells from Angus donors.

“They’ll make sperm carrying Angus genetics, so when they breed by natural cover, the hybrid offspring will be a Nelore and Angus cross. It would be a terminal sire type of breeding system to introduce meat quality traits into the Nelore population by creating a hybrid.”

Oatley acknowledges transferring technology from a research lab into the public domain and later to be used in underdeveloped countries requires either a non-profit or commercial channel for dispersal.

“It comes down to the costs of creating those sires, and what the market can dictate for producers to use it. As an academic, I’d love to find a way to make it as economically feasible as possible, if not free for impoverished regions of the world.”

He believes large challenges other than costs must be addressed.

Federal regulatory frameworks need management. In many countries, CRISPR editing of agricultural traits is undergoing dramatic change.

“The claim is these edits are dramatically different than traditional GMOs. Many of these genetic changes even arise in nature. It’s almost impossible to tell a CRISPR edit versus a natural mutation edit that could have originated in a population. If we’re already eating product from animals with these mutations, putting them in line with CRISPR really doesn’t change that. It’s a more precise way of doing it. There’s a renaissance going on right now in the federal regulatory framework to get these things out into the public to have an impact on how we produce these animals.”

Oatley admits public perception is also a challenge as consumers cling to a negative bleed-over from the GMO era, which was more of an artificial system.

“CRISPR edits don’t do that. They’re just breaking DNA and asking it to repair differently using natural processes in a cell. We need to have a new narrative with the public about what this editing is versus traditional and conventional GMOs.”

Oatley stresses with surrogate sires the end product on dinner plates is not gene edited but animals coming through unedited sperm.

“Only the surrogate vessels delivering those sperm are edited and they’re not targeted for the food chain. All the offspring are unedited.”

People naturally tend to fear what they don’t know and understand, and science content hasn’t always been delivered properly, even in grade schools, he says.

“The more people know about the science and technology, the more comfortable they become with it. Then they’re making informed decisions on what they choose to eat rather than gut or emotional reactions. It’s about improving scientific literacy.”

Oatley says the science has been proven to work and they’re now at the refinement stage, dialing in the surrogate sires for normal fertility and the ability to naturally cover up to 50 females during a breeding season.

“In cattle, we’re probably three years away from a utilizable tool in large scale production. When CRISPR-Cas came on the scene, the floodgates were opened. It changed everything.”

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