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The age of genetically engineered animals has arrived

KEVIN LORIA |

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We're not genetically engineering humans yet. Despite some preliminary experiments to show that it's possible, the process is neither safe nor accurate and we've hardly begun grappling with the ethical and regulatory questions it would entail.

But the technical side of things is changing rapidly. Researchers are already using powerful new technologies to edit the tree of life.

Genetically modified crops are so widespread it's hard to imagine civilization without them.

Genetically modified animals are also more common than most people realize, and we can expect to see even more of these creatures soon — including fine-tuned livestock, designer pets, and even new animals that resemble long-extinct species.

Once we perfect these technologies in animals, the technical barriers to making similar modifications to the human genome will disappear too. Then we'll be left with an even harder question: Where do we stop?

Designer creatures aren't really so new

Humans have been changing the genes of creatures for thousands of years. "We've just called it selective breeding," says Mark Westhusin of Texas A&M, an expert in genetically engineering animals.

The newest gene-editing tools are different from breeding in one fundamental and, many would say, positive way. "We're [now changing traits] in a more targeted way — we actually know what we're doing," says Alison Van Eenennaam, an animal genomics and biotech specialist at the University of California at Davis.

Consider the bulldog with its wrinkled face, the dachshund with its long back, and the pug with its curly tail: animals we've created based on our own preferences. We bred those features into creatures but gave them horrible genetic defects along the way. Bulldogs, with their disproportionately large heads, are all born by C-section, while those other two breeds have serious spine troubles because of their characteristic traits.

All 50 of the most popular dog breeds are predisposed to a genetic disorder, according to a 2009 paper in The Veterinary Journal cited by Emily Anthes, author of "Frankenstein's Cat: Cuddling Up to Biotech's Brave New Beasts."

We've reshaped the world with our breeding of plants and animals and with our own ever-expanding populations. Now we have tools that allow us to make much more accurate changes.

Apples, papaya, corn, soy, and cotton are all genetically modified to be more visually appealing, resistant to disease and pests, and resilient against changing climates. Now, "it's almost like the animal world has caught up to the plant world in terms of our technologies," says Westhusin.

Some fear genetic modification, but is a more accurate method of what we've done for thousands of years really a bad thing?

The new era of genetically modified creatures

The promise of being able to manipulate the building blocks of life on a microscopic level has been with us for a while now.

We engineered the first genetically modified mice in the early 1980s, and soon predicted far more. "The Kid's Whole Future Catalog" of 1982 depicted a scene presumed to be right around the bend: a tiny genetically modified rhino sipping from a bowl next to a wide-eyed and curious cat of the same size.

No such pet rhino exists. But even though it took longer than we thought to get here, the age of genetically modified creatures has now arrived.

A few blocks north of Union Square in New York, in a dark corner of a perfectly ordinary PetCo, a few fish tanks are lit up with blue and black lights. Inside, schools of genetically modified fish are glowing pink and green and striped.

These colorful swimmers first went on sale in 2003, and they are available at pet stores around the United States. They were originally made by transplanting a jellyfish gene for fluorescence into a fish's genetic code. Once the gene was there, it could be passed on, creating a whole new type of creature: a GloFish®.

GloFish® may seem fanciful and silly, but they were originally designed as part of a scientific initiative to make fish that could glow to warn people of dangerous pollutants in the water.

Researchers have transplanted similar flourescence genes into mice, cats, rabbits, sheep, and other creatures, creating almost endless iterations of strangely luminous animals. And that's not all.

Take one recent innovation in livestock. For decades dairy cows have had their horns cut or burned off to prevent injuries to the herd. Now a Minnesota company, Recombinetics, has used genetic manipulation to develop a hornless dairy cow, potentially ending a painful process — if regulators allow these creatures to be used.

Although we could develop hornless dairy cows through breeding, it would take vastly longer and pose more risks. We'd have to mate cows without horns with each other for generations until we got hornless offspring — yet we'd almost certainly lose some of the traits that make dairy cows the best milk producers in the world. It's much easier if you can just disable the genes that code for horns.

Genetic hacks to livestock won't stop with the creation of hornless cows.

Harvard geneticist George Church tells Business Insider his lab is working on making genetically modified pigs that could be suitable organ donors for humans.

Texas A&M's Mark Westhusin tells us his lab has been able to design goats that produce a potential malaria vaccine in their milk.

Researchers are even using the newest technologies to modify embryos from monkeys — animals that are, of course, very similar to humans.

Why things are changing now

A suite of powerful new tools, above all the recently discovered CRISPR-Cas9 system, has given researchers the ability to edit genes with far more accuracy than ever before. As we learn to use these tools and, crucially, as we better understand how a genome actually codes for the parts and characteristics of a creature, the biggest limit to what we can do when reshaping life's blueprint may be our own imaginations.

This recent breakthrough can be attributed to something of a scientific accident. The researchers primarily credited with finding CRISPR-Cas9, Jennifer Doudna and Emmanuelle Charpentier, first encountered the system when studying how bacteria fight viruses. They saw that bacteria sent a small molecule out that would find a specific section of virus DNA and slice it up.

They realized that the precision of that tool could do something else with the correct programming: It could seek out any section of DNA and slice it up. And not only that, if accompanied by other coding material, this process could also replace one section of DNA with a new section of DNA.

This was one of those moments where foundational scientific research turned into a world-changing discovery.

We've had gene-editing technology for decades, but now "we're basically able to have a molecular scalpel for genomes," says Doudna, a biologist at the University of California at Berkeley. "All the technologies in the past were sort of like sledgehammers."

Currently, we can only manipulate traits that are controlled by one or several well-known genes. In time, if we can learn to understand traits that are controlled by dozens or hundreds of genes, we could change just about anything.

As the doorways of possibility open, we don't know what's coming next. Mammoths? Pet dinosaurs? Hybrid monsters? A real unicorn? They're not available at your local pet store, but they're also not quite as far-fetched as they might seem.

Oh, the creatures you'll create

While animals like hornless cows or vaccine-producing goats have clear agricultural or biomedical functions, other researchers want to make creatures with a less obvious use.

De-extinction advocates think bringing back versions of extinct species like mammoths, certain kangaroo rats, and passenger pigeons could have environmental or other benefits. While we can't remake an exact copy of species that are already gone, we could use CRISPR to put genes from these extinct species into their still-living relatives.

In the case of a mammoth, Harvard geneticist George Church is already trying to take the genes that allowed mammoths to survive Arctic cold and put those genes into their closest living relatives, Asian elephants. If they succeed, these new mammoth-like elephants could theoretically repopulate Siberia and Northern Europe, where they'd face fewer threats from development than Asian elephants do in their current habitats.

This could help protect a threatened species of elephant "by extending its habitat range as far north as possible where the land is inexpensive and presents far less conflict over sharing land with farmers," Church tells us by email.

On a more whimsical note, paleontologist Jack Horner spoke to us about the possibility of de-evolving a chicken to create a sort of dinosaur, a "chickenosaurus," if you will. This may sound crazy, but researchers have already used gene-editing tools to make bird embryos with snouts instead of beaks. Replacing wings with hands and tailfeathers with tails isn't that far-fetched.

Horner also said he thought it would be possible to make a unicorn, something that has no ecological need to exist, but that many would find intriguing all the same.

Creating an extremely large or extremely tiny creature — a horse-sized duck or a duck-sized rhino — is complicated, with size being accounted for by potentially hundreds of genes. Many researchers think this is far too complicated to tackle. Others, like Church, say this "illustrates how you can often cut through the complexity. We know how to make very small and very large versions of almost any animal by altering the growth hormone genes."

What if we wanted to make a pig with wings? That would be tricky because we've never seen a six-limbed vertebrate, and so we have no idea what the genetic code for that would look like. "It's really fun to think about ... but the reality is also that learning about the genome is a slow process," says Doudna. "Even if we knew all the genes that were necessary to create a wing, I couldn't predict that they would work properly in a pig to create a wing."

Making creatures that don't serve an important function may be frivolous, but the hundreds of dog breeds and endless varieties of rabbits, cats, fish, and birds that we've developed through breeding are a clear indication of humanity's interest in designing strange creatures for whatever reason.

As Horner reminded us before, "People made Chihuahuas out of wolves, for God's sake." Why not a pet triceratops?

Still: We're talking about learning to write a programming language with millions of letters that we've only begun to learn how to read. It's going to take time.

Should we?

Those who fear that the creation of genetically modified creatures will get out of hand in some sort of irresponsible disaster might remember the quote by Jeff Goldblum's character Ian Malcolm in the first "Jurassic Park" film: "Your scientists were so preoccupied with whether or not they could that they didn't stop to think if they should."

The researchers we spoke with, however, seemed very cautious about tampering with the genetic code.

Pretty much unanimously, when asked about creating some sort of bizarre hybrid creature, leading scientists and researchers in this field responded with, "But why?" It would make more sense to use this new technology "to fix some of the poor animals we have created," suggests Van Eenennaam, "rather than create bizarre new ones."

Even those in favor of bold, risky, projects, like "How to Clone a Mammoth" author and University of California at Santa Cruz Professor Beth Shapiro, want to proceed with incredible caution and ensure that whatever we do, it's done with the goal of creating a more environmentally sustainable planet.

In braving this world of synthetic biology and engineered creatures, Anthes pointed to that ancient Hippocratic oath: First, do no harm.

And yet our understanding of how genomes work is evolving rapidly, and the process of editing genes is easier than it has ever been. Once we know how to make a unicorn or a griffin, someone, somewhere might do it. The part of human nature that makes us want to climb a mountain because it's there is a powerful drive.

Indeed, the process for genetically manipulating an embryo is simple enough that it could be done in a lab you could set up for less than $1,000.

The only thing that's certain is that these radical changes will accelerate, bringing remarkable breakthroughs, fanciful creations, major risks, and new realities we can't begin to imagine today. This is just the start.

Illustrations courtesy of Mike Nudelman, Business Insider. Photos from Aobranc via Wikimedia Creative Commons, Kids' Whole Future Catalog, Scott Bauer for the United States Department of Agriculture, and Nishimasu et al., 2014.