In 2012, 16 pigs genetically modified to excrete less phosphorus waste that leaches into fields and waterways creating ecological dead zones-an environmental boon—were euthanized when the Canadian and U.S. governments signaled approval was not about to come soon. The so-called Enviropigs, which digest their feed more efficiently, lost their funding.
Scientists at the University of Guelph in Ontario developed the first Enviropig in 1999. They genetically engineered swine that could digest the phosphorous compounds in their feed. As a result, wrote Jef Akst in The Scientist, “the manure produced lower levels of phosphorus, notorious for leaching into groundwater beneath pig farms and fueling algal growth in local streams and lakes.”
The research team applied for approval to sell the animals for human consumption in the U.S. in 2007 and Canada in 2009. Initial reviews of the application were positive but over time, neither the Food and Drug Administration nor Health Canada acted on the application. The project ran out of money, and died.
As Akst noted, anti-GM activists argued that, because of their low-phosphorus manure, if the Enviropigs were approved for human consumption, “big, bad agriculture [would have] an excuse to put them in even more concentrated facilities,” says Alison Van Eenennaam of the University of California, Davis, who studies how DNA technologies can be applied in the beef-production industry. “They really targeted it and made it a bad thing.”
Now, technological advances are leading the field of animal biotechnology away from classic genetic engineering to more novel techniques that some hope will break the innovation log jam. The advances include cloning techniques and the advent of designer and programmable nucleases, special proteins that enable a powerful approach known as gene editing, or genome editing. In addition to improving yield as sources of milk and meat, the new techniques can open a range of new possibilities, like making antibodies for disease treatment, or producing human milk (as opposed to cow milk).
Genetic modification can turn cows into factories of products other than for just making milk. Whether from humans, or cows, it’s normal for milk to contain antibodies. Because human milk contains a class of antibodies known as IgA, infants who nurse are protected better compared with infants given only formula for the first few months after birth. Nursing infants also are protected because human milk contains lysozyme, which has antimicrobial activity. Modifying cows to secrete not only more humanized nutritional proteins in the milk, along with lysozyme, the new techniques open new possibilities in infant nutrition. At the same time, because milk is a convenient secretion for supplying antibodies, cows are now getting a lot of attention as potential factories for various antibodies, include those used in a treatment for Ebola.
Avoiding regulatory difficulties
Advances in cattle cloning revolve around two related techniques: somatic cell nuclear transfer (SCNT) and somatic cell chromatin transfer (SCCT). These techniques, which do not fall under regulations currently strangulating advances in agricultural biotechnology, can make embryonic stem cell approaches obsolete and cloned cells can be used to create complex genetic modifications in cattle, yet without transgenic material. The programmable nucleases for gene editing have complex names and abbreviations, like “ZFNs”, “TALENs”, and “CRISPR/Cas9”. Essentially, however, they’re like molecule surgeons. They can get inside cells and snip genes in DNA at very precise locations. Used together with special types of RNA (a molecule similar to DNA), this allows for accurate cutting and pasting of virtually any sequence in an animal’s genome, and that’s why it’s referred to as “editing”.
Unlike techniques that depend on transfer of so-called foreign genes (transgenic techniques), gene editing and other non-transgenic strategies would not necessarily trigger intense regulatory review under current federal guidelines. This is important, because the approval process for transgenic animals (in contrast with plants) typically is extremely difficult in North America. To appreciate just how difficult, consider the genetically engineered salmon AquaBounty. Currently, the only other pending animal biotechnology approval in process, the salmon has been swimming around in this status for 19 years. The Genetic Literacy Project’s Jon Entine wrote a expose of the Obama Administration’s political delaying tactics on the AquaAdvantage salmon for Slate two years ago, which led to the immediate publication in the Federal Register of a request for public comment on a draft environmental assessment for AquaBounty’s genetically modified salmon. Then the process stalled again, reportedly from pressure from the White House–and perhaps from objections by the Obama family chef, an organic activist.
In January, 2009, the Food and Drug Administration issued a final guidance for industry on the regulation of genetically engineered (GE) animals, but so far that appears mostly for show–no animals genetically engineered using classic GE technology have been approved and there are none in the pipeline.
Foot dragging on the AquaBounty approval by the Administration and regulatory officials prompted more than 50 scientists and interested parties to send a letter sent to the White House in 2012.
There is much more at stake here than just a fish. The inexplicable regulatory bottleneck that has been encountered by the AquAdvantage salmon suggests that the FDA’s science-based regulatory review process for the products of animal biotechnology has no predictable timeline and is holding up the development of an industry that promotes economic growth, innovation, competitiveness, and job creation in the United States.
There is skepticism whether the new generation of animal biotechnology innovation, including gene editing, will be treated much differently, and for this reason transgenic animal research has fled to other countries. China has launched an $800 million public-private investment into transgenic animals, and genetically modified animals are being developed in India, New Zealand, and across Latin America, including in Cuba. But North America has become a dead zone.
James Murray, an animal scientist at the University of California–Davis has developed goats that make milk with diarrhea-preventing lysozyme, a bacteria-fighting protein that could save children’s lives. With no government or private money on the horizon, he’s set up his lab in Brazil, a more biotech-friendly locale.
“When you don’t have a regulatory pathway forward and the government doesn’t support research in this area, what company will invest in this field?” he asked. “None. The AquaBounty situation is just confirmation of a hopelessly politicized process.”
The future of animal genetics is so dire, universities are killing off courses. “My program started off doing genetic engineering,” said Van Eenennaam, who co-authored a scathing article for Nature Biotechnology on the broken approval process. “I couldn’t get any government funding for my work in this area, so I shut the program down. Why would I train graduate students for jobs that won’t exist?”
To assure that any innovative animal product is not dead in the water as soon as it’s introduced, it’s important that transgenic techniques are not used to make it. This is not a point of ideology, but mere practicality, given the current regulatory environment. By avoiding the need for foreign genes, cloning and gene editing strategies can open a range of possibilities, though in uncharted territory there’s always some risk. Thus, while the new techniques potentially can be a boom for animal biotechnology, they also could turn out to be a bust, but that risk is probably worth taking given the virtually limitless potential of the technology.
David Warmflash is an astrobiologist, physician, and science writer. Follow @CosmicEvolution to read what he is saying on Twitter.
