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http://undark.org/article/gmo-goats-lysozyme-uc-davis-diarrhea/

The next day her students will isolate and amplify a portion of the goat’s DNA that scientists at Davis have genetically altered to code for human lysozyme, an antimicrobial enzyme commonly found in people’s tears, saliva, and breast milk. Lysozymes work on the front lines of the immune system, destroying bacterial cells that cause diarrhea and other infections.

Not long ago, what Maga and her colleagues were doing seemed revolutionary, given diarrhea’s enormous global toll. According to the World Health Organization, 525,000 children under five died last year from diarrheal diseases, mostly in poor communities in developing nations where waterborne diseases are rampant and vaccines and antibiotic treatments are difficult to acquire and distribute. That’s more childhood deaths than AIDS, malaria, and measles combined.

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They now have the data to prove it many times over, Maga and her colleagues say. But the world, it would seem, isn’t ready for it.

Instead, the researchers have run headlong into the pitched, prolonged, and, critics would argue, misguided first-world debate over genetically modified organisms, or GMOs. It’s a conflict animated in large part by a rapidly evolving arsenal of genetic engineering tools and the inability of both policymakers and the public to quickly and effectively make sense of it all — or even to apprehend the full spectrum of motivations for manipulating genes, from the mercenary and commercial to the humanitarian. This has left the UC Davis goats, along with a host of other transgenic animals with the potential to curb disease and save lives, in a regulatory limbo — even as other genetically engineered organisms, from corn to fish, earn regulatory approval.

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The gene of interest to the UC Davis team is called HLZ, and it is a relatively recent addition to the goat genome. Maga and her colleagues at Davis successfully introduced it roughly 20 years ago, through a process called pronuclear microinjection. The result was Artemis, born in this same barn on a spring morning in 1999. She had a streak of black on her hind flanks, bright eyes, and something no goat had ever had: the ability to produce human lysozyme in her milk.

Regulating biological innovations has turned out to be a complicated affair — particularly because the policies that would govern advanced biotech were developed a long time ago.

Since then, the human gene in her DNA has been passed on through generations of goats who have spent their lives in the Davis herd, down to some of the ten kids just born. Because of Mendelian inheritance, they won’t all have the gene, which carries with it both tremendous potential to do good and the stigma that comes with the term GMO.

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Lysozyme occurs naturally in the milk of all mammals, but it’s especially concentrated in human breast milk: 1,600 to 3,000 times the amount found in livestock milk. Murray and Maga hypothesized that if they could engineer goats to make extra HLZ, they could give the milk to non-nursing infants and young children at risk for diarrhea in effect, restoring the protective effects of breast milk. With a grant from the UC system they developed Artemis, and built a herd from her progeny. In the spring of 2004, once they had female goats producing the extra lysozyme, they started looking at the milk’s effects on pigs (which are closer to humans than mice). The results were immediate: The milk changed the type of bacteria in the pigs’ guts, significantly reducing disease-causing pathogens. Their intestines also looked healthier, with more surface area for better nutrient absorption. Maga was elated. “I thought, ‘Wow, this might really work!’” she says, remembering the results.

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Maga inoculated pigs that mimicked these physical features with an E. coli infection, then fed some of them HLZ goat milk. Those pigs recovered remarkably faster, with less damage to their intestines.

She was triumphant. Here it was, a highly effective way to combat a major cause of childhood mortality, and all you needed was a very special goat. The Gates grant also offered successful projects the opportunity to receive follow-up funding to further develop the concept. So she applied. Her data was strong, the results compelling. It was exactly the sort of thing the Gates Foundation would be interested in backing — a low-cost, scalable remedy for a public health problem with huge implications for populations in developing nations.

Her application for funding was rejected. In the email she received in April 2014, the foundation provided some mild scientific critique, along with the suggestion that the hurdles in public acceptance of GMOs were simply too high to warrant the testing of “only a single human antimicrobial protein for diarrhea prevention.”

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And that raises still another problem. Diarrhea claims the lives of very few Americans. It’s prevalent in places like sub-Saharan Africa, South America, and Southeast Asia places where upwards of 60 percent of the population are farmers, places where it would be far easier to raise a transgenic goat than to store, transport, and administer a drug isolated from one. So consumers in the First World are distanced from any direct advantages of products derived from genetic technologies. The opposition to them reflects not so much a presence of risks but an absence of benefits at home. Van Eenennaam laments that those in well-off countries don’t care about the 25,000 people who die from starvation every day. “I think it’s activist pressure on politicians that drives these decisions,” she says, “which is why we need applications that the general public understands.”

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Animal researchers are seizing the opportunity to reimagine the genomes of an entire menagerie of creatures, not just for medical models and drug production. For the first time in years, scientists are urgently investing time and money in next-generation livestock. Projects underway include chickens that produce only female offspring. According to the animal rights group Mercy for Animals, more than 200 million day-old male chicks are now killed in grinders each year by the egg industry, which needs many more hens than roosters. Van Eenennaam is working on a line of bulls that would produce all-male herds of cattle to improve beef production efficiency. Also on the way are more hygienic honeybees, better-muscled sheep, and a host of animals that won’t need antibiotics because they’ll be born resistant to disease. This flurry of research represents a concerted movement by scientists to show the usefulness of the technology while there’s still time to influence regulators.

At the Roslin Institute in Edinburgh, Scotland, Bruce Whitelaw has changed three parts of one gene in domesticated pigs to make them more like wild pigs that are resistant to the devastating African swine fever. Though it’s not year clear whether they are resistant, those animals are already on the ground in Britain, thanks to investments from a commercial partner (The European Union is expected to rule on the regulatory status of gene editing within the year). Whitelaw says the agricultural industry’s recent interest in gene editing indicates a major shift in momentum the last three years. “What editing will do is increase, dramatically, the number of projects coming through,” he says. “The application numbers will be skyrocketing, and they [regulators] will need to do something about it.”

It's a really long read, but a very rewarding one, and it gives you so much insight into the world of genetic engineering and the potential it holds, but also the difficulties it faces.


GAF, what are your thoughts? What do you think about having these goats, and other genetically modified livestock, help save lives?