Meet the Woman Using CRISPR to Breed All-Male “Terminator Cattle”

Meet the Woman Using CRISPR to Breed All-Male “Terminator Cattle”

ben January 10, 2018 0

A graduate student was waiting for Alison Van Eenennaam in the doorway of her lab at the University of California, Davis. An Australian geneticist, she spends days on the road arguing with critics of Monsanto’s GM soybeans, appearing in documentaries, and telling the public why genetic modification is safe.

Her scientific work, though, involves cattle. Now, as the student, Joey Owen, whispered something in her ear, she let out a hearty “Yeaaaah” in her Down Under drawl. “We have knock-in!”

After a year of trying, the lab had just used the gene-editing tool CRISPR to add a gene called SRY to some bovine skin cells. And SRY is no ordinary bit of DNA. All on its own, the presence of SRY can make a female turn out to be essentially male—with bigger muscles, a penis, and testicles (although unable to make sperm).

“This is not a normal day in the lab,” Van Eenennaam said.

Gene-editing technology has big potential in farm animals. It has been used to create pigs immune to viruses and sheep whose wool grows longer. Van Eenennaam participated in a successful effort to edit dairy cows to eliminate their horns.

Now, in the project she calls “Boys Only,” she aims to create a bull that will father only male offspring: either normal bull calves or ones with two X chromosomes but also the male-making SRY. No females at all.

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That would be valuable to beef ranchers, she thinks, because males grow bigger and faster. It’s that much more steak. Beef is already America’s most valuable farm product. Imagine, she says, CRISPR bulls roaming the pastureland, skewing the odds toward maleness and making the industry more efficient.

“That’s why I fight for innovation in animal breeding,” she says. “It’s free, once you’ve made the genetic improvement.”

Regulatory problems

Van Eenennaam is a staunch advocate of GMOs in all their forms. As a female scientist and a mother, she can be tough to argue with on issues like food safety. In 2014, along with Monsanto’s chief scientist, she vanquished skeptics in a public debate attended by science personality Bill Nye.

The GMO debate, ironically, has had its most chilling effects on animal scientists like Van Eenennaam, who holds the title “cooperative extension specialist.” The job is to spread practical scientific know-how to farmers. Yet that’s proving almost impossible to do. Only a single gene-modified species—a super-fast-growing salmon—has ever been approved for consumption in the U.S.

Scientists hoped gene-editing might get a lighter touch from regulators, speeding new ideas into the food chain. But in January 2017, as one of the Obama Administration’s last acts, the U.S. Food and Drug Administration said it intended to treat CRISPR-edited animals as if they were new drugs, requiring elaborate and costly safety studies.

The proposed rules “put a huge regulatory block on using this gene-editing technique in animals,” says Van Eenennaam, who fired off a seven-and-a-half-page single-spaced letter to the FDA, questioning the decision.

Learn more about how CRISPR works.

Companies are now lobbying the Trump Administration to kill the rules and declare gene-edited animals unregulated. They’ve warned the White House the U.S. could fall behind countries like Argentina and Brazil.

Some even expected President Donald J. Trump to announce the change this week during a live address to farmers in Nashville. Instead, Trump offered a more general promise about “streamlining regulations that have blocked cutting-edge biotechnology, setting free our farmers to innovate, thrive, and to grow.” 

Terminator seed

The advent of CRISPR—a new kind of molecular scissors that can precisely cut DNA—has made it far easier to alter the genes of just about any organism. But fears of runaway technology mean it’s easier to win funding to study CRISPR’s risks and dangers than to do anything useful with it.

Van Eenennaam, in fact, got the funding for the cattle project from a U.S. Department of Agriculture program looking at the potential hazards of gene-modified organisms. The department wants ways to sterilize GM organisms, including catfish and poplar trees, so their DNA modifications don’t spread to wild relatives.

Because animals turned male by SRY are expected to be sterile, they won’t pass on the genetic change, or any other DNA alterations linked to it. That offers a form of “genetic containment.”

“It’s basically ‘terminator’ technology,” Van Eenennaam says, referring to an idea once floated by agricultural giants to create plants with sterile seeds so farmers couldn’t collect and replant them. That was “the line we argued that got it funded.”

The original terminator proposal proved controversial. So much so that in 1999 Monsanto pledged never to commercialize sterile GM plants. (Instead, farmers sign contracts agreeing not to save seeds.) Even though it was abandoned, the idea proved notorious enough that GMO critics are still talking about it.  

“I hate to use that term, because activists have always said “Oh my God, Monsanto’s using terminator technology’ and they never did.” says Van Eenennaam. “I want to have a more nuanced discussion around this technology, rather than just the same-old same-old … That’s just like, ‘Ugh, shoot me.’ We are being blocked from using these technologies because of the discussion around the crops.”

Ersatz males

Because cattle are tagged, branded, corralled, and slaughtered, as well as being slow to reproduce, they’re actually among the least likely organisms to cause a genetic escape. Van Eenennaam’s long-term goal is to make beef production more efficient. Males yield more meat than females and don’t get pregnant or go into heat. She thinks the ersatz males should be about 15 percent more efficient at turning grass and grain into muscle than females.

To create them, her lab is zeroing in on SRY, also known as testis-determining factor. In mammals, this gene on its own can determine whether an animal is physically male. As you’d expect, it’s normally located on the Y chromosome.

Sometimes, though, the gene naturally jumps over to the X chromosome. It can happen to humans. In 1992 the International Olympic Committee started testing female athletes for SRY, finding about 13 cases among more than 5,000 women, though mandatory sex testing was later abandoned as intrusive and potentially unfair.

So far, no female-turned-male bovine has ever been found to naturally harbor SRY. Owen, her student, thinks it could have happened without anyone noticing: most male beef cattle are castrated anyway.

Van Eenennaam’s lab aims to create a bull with an extra copy of SRY edited onto its X chromosome so any daughters will end up with it. The day I visited, Owen reported the first step: adding SRY to an X chromosome in male skin cells. To make a living bull, Van Eenennaam needs to create a similar edit in a cattle embryo. If that doesn’t work, she can use a skin cell in Owen’s petri dish to make a bull by cloning.

Cattle breeders already have a way to make only males. Because a sperm cell bearing a Y chromosome has slightly less DNA than its X counterpart and is thus lighter, bull semen containing these cells can be separated by weight. All-male semen is sold in catalogues.

But terminator bulls could be a better solution. Artificial insemination is used in only about 4 percent of beef cattle because of the effort involved in roving the range, gathering cows, and getting them pregnant. Van Eenennaam thinks her male-only bulls would be a less expensive way.

“A bull is a lot better at doing it than we are,” she says. “And he enjoys it a lot more.” 

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