Will Human-Animal Hybrids Make Medicine or Monsters?

The quest to build better people.
May 13 2013 7:45 AM

Manimal Rights

How far should science go in making human-animal chimeras?

Mice during a demonstration at The 2nd International Conference of Israel Homeland Security expo on November 12, 2012 in Tel Aviv, Israel. Israels Tamar Group has developed an explosives and drugs detection system, named Bio Explorer, using mice.
It may not be so long before we're faced with some hairy bioethics: What rights should we assign to mice with human brains?

Photo by Uriel Sinai/Getty Images

Attention, sane and insane scientists: Your experiments to create half-men, half-beasts may not be legal in every jurisdiction. The construction of such hybrid life forms is now prohibited in several Sun Belt states, including Arizona and Louisiana, and Mississippi lawmakers have introduced a bill to do the same.

Daniel Engber Daniel Engber

Daniel Engber is a columnist for Slate

These regulations have become a hobby-horse of the religious right, and so an endless source of mirth for science-minded lefties who think they have the better grasp of biotechnology. "Mississippi Bill Would Ban Manimals, Mermen, and Minotaurs," according to a blogger at Mother Jones. Republicans are scared of "some sort of human-brained lion with bear paws," said a writer at Daily Kos, "because scientists are this close to doing that just for the flying hell of it."

This knee-jerk sarcasm is no less embarrassing today than it was in 2006, when progressives piled on President Bush for mentioning "human-animal hybrids," among other "egregious abuses of medical research," at the back-end of a State of the Union address. Jon Stewart called that digression a "brief stop in Crazytown;" BoingBoing mocked him with a T-shirt.

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For all the hee-haws, though, this Republican agenda item speaks to something very real in bioscience. Human cells or DNA are planted into laboratory animals as a matter of routine, and nonhuman parts end up in people, too. Both forms of interspecies mixing—from us to them, and them to us—hold tremendous opportunities for therapy and could lead one day to biological enhancement. But they also bring to light some important moral quandaries.

The word hybrid, in the scientific sense, describes an organism that carries DNA from different species in each of its cells. Human-animal combos of this kind have indeed been created by several different labs—though only at the very early stages of development, and never in the hopes of making full-grown, crossbred monsters. For an old-fashioned test for male fertility, doctors would try to fertilize a set of hamster eggs with a patient's sperm. (If they succeeded, the hybrids would be destroyed.) More recently, British scientists implanted cow eggs with nucleic acids drawn from human skin as a means of growing human stem cells in a dish. (The constructs would never progress beyond this point.)

True hybrids may be rare, but lab-made chimeras, in which cells from two strains or species coexist in a single organism, are utterly ubiquitous. To engineer the genome of a mouse—the starting point for many biomedical experiments—scientists must generate a chimeric blend of different breeds.

Human-mouse chimeras are somewhat common, too. Since the early 1990s, researchers have been replacing mouse liver cells with human equivalents. These lab-created organisms might provide for more effective drug-testing, as the rodents' "humanized" livers can metabolize a medicine in a way that's more like ours. (For the moment, this utility is more theoretical than practical: No one has yet proven that human-mouse chimeras actually improve toxicology testing.)

Mice with human livers are just the start. "It's all about humanized right now," said the CEO of one of the leading mouse breeders in the world when I visited his facility in 2011. Not long ago, Chinese scientists embedded genes for human milk proteins into a mouse's genome and have since created herds of humanized-milk-producing goats. Meanwhile, researchers at the University of Michigan have a method for putting a human anal sphincter into a mouse as a means of finding better treatments for fecal incontinence, and doctors are building animals with humanized immune systems to serve as subjects for new HIV vaccines.

The hybrid-haters in the GOP understand the value of these experiments, and they've taken pains to separate the useful from the creepy. The laws passed in Arizona and Louisiana, like the federal bill that ex-Rep. Sam Brownback tried and failed to pass in Congress, attempt to provide some nuance. They say it's fine to make transgenic animals laced with human genes, and generally OK to build chimeric animals with implanted human organs, tissues, or cells. Even in the states where manimals and minotaurs are banned, scientists can humanize a mouse by giving it a person's liver or immune system.

But the regulations try to draw the line at full hybrids—where animal eggs are fertilized with human sperm or vice-versa. And they also ban the use of chimeric animals with human brains. These aren't right-wing talking points so much as common ethical intuitions. It's OK to mess with a creature's "simple" parts—the plumbing in its gut, let's say—but we're risking moral crisis when we start to humanize its neural tissue.

Nonpartisan expert commissions have reached the same conclusion. After two years studying the issue, the British Academy of Medical Sciences released a report in 2011 that found people would be uneasy over interspecies mergers that looked or acted human or had a human-like brain.

Yet experiments like these are going forward just the same. In just the past few months, scientists at the University of Wisconsin and the University of Rochester have published data on their human-animal neural chimeras. For the Wisconsin study, researchers injected mice with an immunotoxin to destroy a part of their brains—the hippocampus—that's associated with learning, memory, and spatial reasoning. Then the researchers replaced those damaged cells with cells derived from human embryos. The cells proliferated and the lab chimeras recovered their ability to navigate a water maze.

For the Rochester study, researchers implanted newborn mice with nascent human glial cells, which help support and nourish neurons in the brain. Six months later, the human parts had elbowed out the mouse equivalents, and the animals had enhanced ability to solve a simple maze and learn conditioned cues

These protocols might run afoul of the anti-hybrid laws, and perhaps they should arouse some questions. These chimeric mice may not be human, or even really humanish, but they're certainly one step further down the path to Algernon. It may not be so long before we're faced with some hairy bioethics: What rights should we assign to mice with human brains?

All that has to do with sticking human parts in beasts. Transplants also go the other way: Heart valves and ligaments can be extracted from a pig, stripped of excess porcine cells, and implanted in a person. In the not-too-distant future we may see more substantive forms of xenotransplantation, particularly from pigs that have been genetically engineered to make their parts more amenable to human use. (These animals lack a pig-specific protein that induces a strong immune response from people.) Transplanted pig corneas and pancreatic cells will be next, and we might see hearts and kidneys one day as well.

These procedures haven't generated much angst, except perhaps from orthodox rabbis. Presumably that's because they'd leave us with a fully human brain, and that's where we like to think our deepest personhood resides. Transplanted pig parts also fail to violate a taboo against enhancement: They're therapies, not upgrades—a way to mend a broken part.

What if animal organs, cells, or DNA could make us faster, stronger, or more adept? The Department of Defense has dabbled with the notion of dosing humans with bacteria taken from a pig's digestive tract. This research program, known as "Intestinal Fortitude," could in theory help a solder to digest cellulose or otherwise survive on "non-traditional foodstuffs."

No one has transfected a living human with nonhuman genes in an effort to bestow cheetah-speed or night vision, or tested radioactive spider-bites in a controlled, laboratory setting. "Let's put it this way," says Maxwell Mehlman, a bioethicist at Case Western and author of a book on transhumanism, "we can't even figure out a good way of gene doping using human genes."

One hundred years ago, a doctor named John Brinkley started implanting patients with goat testicles as a way to make them virile. These days, quack physicians promise to invigorate us with deer antlers. The technology may change, but the dream of manimal enhancement never goes away.

Read more from Slate’s Superman package: Is human enhancement cheating, everyday technologies that already give us superpowers, and would you use superpowers for good or evil?

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