It was after a home invasion almost a decade ago that David Ishee first got interested in breeding dogs. A burglar with a gun had broken into his home in Jackson, Mississippi, where Ishee was asleep along with his wife, 3-year-old-daughter and newborn son. Ishee pulled out his own shotgun and scared the would-be thief off. But he was unsettled wondering what might have happened had he not been around.
Ishee wanted a guard dog, and giant, docile mastiffs are good ones to have around little kids. Like so many carefully bred dogs, though, mastiffs are riddled with genetic disorders. So Ishee decided to start breeding them himself, with plans to increase their genetic diversity and hopefully make them healthier, happier and more fit. Over just a few generations, he saw results. Gone was the sagging skin and oversized head that makes so many mastiffs look goofy. He told me his dogs could jump higher and run faster than most other Mastiffs can.
But because the majority of the genetic disorders dogs suffer from are recessive, Ishee could not simply breed them out. Last year, he decided to try genetic engineering after watching a TED talk about scientists creating glowing plants. Using cutting-edge genetic engineering technology like CRISPR, could he do the same thing to his dogs at home?
"My dogs are healthy, but they are still probably carrying genes for all kinds of diseases," Ishee told me. "To produce not just a healthy dog but a truly healthy population, you have to be able to totally get rid of those diseases somehow."
Ishee is 30 and lives on a few acres of land in the Mississippi countryside, where, when not breeding dogs, he makes a living as an operator at an oil field plant. His daughter was born when he was 18, so after getting his GED he didn't have the time or the money to go to college. He didn't know much about genetic engineering, but he knew a lot about dogs.
It's also worth mentioning that Ishee is a pretty huge nerd. All of his dogs are named for mythological creatures, like Osiris, the Egyptian god of the afterlife. His breeding operation, Midgard Mastiffs, is named for one of the Nine Worlds of Norse mythology.
Ishee started messing around, trying to grow bacteria using Jell-O and bouillon cubes. Eventually he called Josiah Zayner, a synthetic biologist who left NASA to sell CRISPR kits to the masses and hopefully spur a biohacker revolution.
With less than $1,000 and some advice from Zayner, he joined the growing ranks of DIY gene hackers, building a lab in his shed capable of basic genetic engineering. He ordered some DNA for Photorhabdus luminescens, a bioluminescent bacteria, off the internet and cultivated it in his lab. Then he took sperm from a male dog, and, using a technique called sperm-mediated gene transfer, infused it with genes from the glowing bacteria. This glowing sperm concoction is what he eventually used to impregnate a female dog, with the hope of making puppies that glow.
"It's basically artificial insemination with a few steps in the middle," he told an audience recently at a biohacker conference. "Breeders do artificial insemination already all the time."
His dog is now pregnant. She's due in October.
"Hopefully, then we'll have some glowing puppies," he told me.
Ishee's goal, of course, isn't just to make glowing Frankenpuppies. The glowing puppies are just proof of concept. Eventually, he wants to sequence the genomes of all of his dogs to check for common genetic conditions among Mastiffs like hip dysplasia and thyroid problems and then figure out how to engineer them out. Then he wants other breeders to start doing the same thing. (A biohacker friend joked that Ishee wants to "open-source puppies.")
"We have the technology to solve these problems, but no one in the science community has an interest in solving them in dogs. Dog breeders have interest but they don't know how to do it," he told me. "This is an incredibly useful technology. There's no reason we should be breeding dogs in the same way we did thousands of years ago."
His grand vision is to overturn the damage of decades of breeding dogs that are too closely related, and create populations of dogs free from genetic disease.
"I want to make perfect dogs," he told me. "I don't want slightly imperfect dogs."
Of course, creating genetically perfect canines or even ones that simply glow in the dark is not as easy as cultivating bacteria with Jell-O.
Ishee's next litter of puppies will theoretically have the right genes to make them glow, but that doesn't mean that they actually will. For one, the light the bacteria he used emits is blue-green, which means it might get absorbed by the puppies' reddish interiors. Or something could interfere with his genetic addition to silence the new genes completely.
"Realistically, they may not glow," he said. "I think the best case scenario is that if you sit in a dark room and let your eyes adjust, you will see them faintly glow a little bit."
To get actually glowing puppies will likely take much tweaking—say making the genes glow red instead of blue perhaps—if he can ever get them to emit visible light at all.
Editing out disease will be even trickier. With just a PCR machine and a few dollars, Ishee can start testing his dog's DNA for specific genetic conditions. But to eventually sequence their entire genomes will take much more time and money. And exactly how to fix each condition in question will not be as obvious as simply snipping out one or two genes. Biology is complicated. Sure we have used CRISPR to edit muscular dystrophy and HIV out of mice, but even in fully funded university labs scientists frequently are stymied by unforeseen obstacles and off-target effects.
The glowing plant project that inspired Ishee suffered exactly this fate. DNA, the project's founders argued is just computer code and biology hardware. They envisioned “a world where bio-engineering is as easy and commonplace as mobile application development is today.” But after raising $484,013 on Kickstarter to create bioluminescent plants visible at night, years later the company still has not perfected plants that emit light. The project had been based on the work of Alexander Krichevsky, a scientist who made tobacco plants dimly glow in 2010. But Krichevsky had all the tools of a well-funded university lab, and still years later has not figured out a way to make plants grow brightly enough to interest consumers. You may have heard of animals that glow before, but most of the "glowing" critters that have grabbed headlines are actually fluorescent, not bioluminescent.
Ishee is well aware of how absurd his quest sounds. But he's convinced that with enough time and effort, he'll eventually figure it out.
On his iPhone, Ishee showed me photos of what mastiff breeds like Great Danes and bulldogs used to look like hundreds and thousands of years ago, before they'd undergone so much human intervention.
"Mastiffs are just totally abused by breeders," Ishee told me. "Constantly breeding dogs that are unhealthy, that's animal abuse.:
While glow-in-the-dark puppies sound futuristic, it's just a proof of concept. What Ishee's really trying to do, he told me, is take the DNA of mastiffs "back in time."
"I'm terrible at art, unless you count living things," he told me. "These dogs are my attempt at making a masterpiece."