A graduate student stood at the entrance of Alison Van Eenennaam's laboratory at the University of California, Davis, awaiting her arrival. An Australian geneticist, she spends much of her time traveling to debate critics of Monsanto's genetically modified soybeans, appearing in films, and educating the public on the safety of genetic modification.
However, her own research centers on cattle. When the student, Joey Owen, leaned in to share news, she responded with an enthusiastic "Yeaaaah" in her Australian accent. "We have knock-in!"
After twelve months of persistent effort, the lab had successfully employed the CRISPR gene-editing tool to insert a gene known as SRY into bovine skin cells. SRY is no typical piece of DNA. Its mere presence can transform a female into what is essentially a male—featuring larger muscles, a penis, and testicles (though infertile).
"This isn't an ordinary day at the lab," remarked Van Eenennaam.
Gene-editing technology holds tremendous promise for farm animals. It has already been used to develop pigs resistant to viruses and sheep with extended wool growth. Van Eenennaam took part in a successful initiative to edit dairy cows so they no longer grow horns.
Currently, in a project she calls "Boys Only," she aims to produce a bull that fathers only male calves—either normal bull calves or those with two X chromosomes but carrying the male-determining SRY. No female offspring would be produced.
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This would be highly advantageous for beef ranchers, she argues, since males grow larger and more rapidly. That translates to more steak. Beef is already America's most valuable agricultural commodity. Imagine, she says, CRISPR bulls roaming pastures, shifting the odds toward male births and enhancing industry efficiency.
"That's why I advocate for innovation in animal breeding," she states. "It's free once you've made the genetic improvement."
The Woman Behind the Push for All-Male "Terminator Cattle" via CRISPR
Regulatory Hurdles
Van Eenennaam is a strong proponent of GMOs in all forms. As a female scientist and mother, she presents a formidable argument on food safety issues. In 2014, alongside Monsanto's chief scientist, she defeated skeptics in a public debate attended by science personality Bill Nye.
Ironically, the GMO debate has had its most severe impact on animal scientists like Van Eenennaam, who holds the title "cooperative extension specialist." Her role involves disseminating practical scientific knowledge to farmers. Yet this has become nearly impossible. Only one genetically modified species—a fast-growing salmon—has ever received U.S. approval for consumption.
Researchers hoped gene-editing might face lighter regulatory scrutiny, accelerating the introduction of new ideas into the food supply. However, in January 2017, as one of the Obama Administration's final actions, the U.S. Food and Drug Administration declared its intention to treat CRISPR-edited animals as new drugs, requiring extensive and costly safety assessments.
The proposed regulations "create a massive regulatory barrier to using this gene-editing technique in animals," says Van Eenennaam, who sent a seven-and-a-half-page single-spaced letter to the FDA questioning the decision.
Companies are now lobbying the Trump Administration to scrap these rules and declare gene-edited animals exempt from regulation. They've warned the White House that the U.S. could fall behind countries like Argentina and Brazil.
Some anticipated President Donald J. Trump would announce this change this week during a live address to farmers in Nashville. Instead, Trump made a broader pledge to "streamline regulations that have blocked cutting-edge biotechnology, freeing our farmers to innovate, thrive, and grow."
Terminator Seed Concept
The arrival of CRISPR—a novel type of molecular scissors capable of precisely cutting DNA—has made it much simpler to alter the genes of nearly any organism. Yet fears of uncontrolled technology mean it's easier to secure funding for studying CRISPR's risks than for applying it beneficially.
Van Eenennaam actually obtained funding for the cattle project from a U.S. Department of Agriculture program focused on the potential hazards of genetically modified organisms. The department seeks ways to sterilize GM organisms, such as catfish and poplar trees, to prevent their DNA modifications from spreading to wild relatives.
Because animals masculinized by SRY are expected to be sterile, they won't transmit the genetic change or any associated DNA alterations. This provides a form of "genetic containment."
"It's essentially 'terminator' technology," Van Eenennaam says, referencing an idea once proposed by agricultural giants to create plants with sterile seeds, preventing farmers from saving and replanting them. That was "the line we argued that got it funded."
The original terminator idea proved highly 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 concept remains notorious enough that GMO critics still discuss it.
"I hate using that term, because activists have always said 'Oh my God, Monsanto's using terminator technology,' and they never did," says Van Eenennaam. "I want a more nuanced conversation about this technology, rather than 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."
Synthetic Males
Since cattle are tagged, branded, corralled, and slaughtered, and reproduce slowly, they are actually among the least likely organisms to cause a genetic escape. Van Eenennaam's long-term objective is to make beef production more efficient. Males yield more meat than females and don't become pregnant or go into heat. She believes these synthetic males should be about 15 percent more efficient at converting grass and grain into muscle than females.
To create them, her lab is focusing on SRY, also known as testis-determining factor. In mammals, this gene alone can determine whether an animal develops as male. As expected, it is typically located on the Y chromosome.
Sometimes, however, the gene naturally jumps to the X chromosome. This can occur in humans. In 1992, the International Olympic Committee began testing female athletes for SRY, finding about 13 cases among over 5,000 women, though mandatory sex testing was later abandoned as intrusive and potentially unfair.
So far, no female-turned-male bovine has been found to naturally carry 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 inherit it. The day I visited, Owen reported the first step: adding SRY to an X chromosome in male skin cells. To produce a living bull, Van Eenennaam needs to create a similar edit in a cattle embryo. If that fails, she can use a skin cell from Owen's petri dish to generate a bull through cloning.
Cattle breeders already have a method to produce only males. Since a sperm cell carrying a Y chromosome has slightly less DNA than its X counterpart and is therefore lighter, bull semen containing these cells can be separated by weight. All-male semen is available in catalogs.
But terminator bulls could offer a better solution. Artificial insemination is used in only about 4 percent of beef cattle due to the effort involved in roaming the range, gathering cows, and impregnating them. Van Eenennaam thinks her male-only bulls would be a more cost-effective approach.
"A bull is much better at doing it than we are," she says. "And he enjoys it a lot more."
